FEBS Letters RSS feed: Articles in Press. FEBS Letters is one of the world's leading journals in biochemistry and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, hypotheses and research letters that merit urgent publication. FEBS Letters offers: • Faster publication: ? Accepted articles are published online in 3 days ? The print version of the article is published in 3 to 5 weeks after acceptance • Full-text article disclosure in HTML and PDF formats • Articles in Press are included in PubMed • Easy online manuscript submission system • Transparent online peer review and manuscript tracking system • No page charges • Free color figures Subject Coverage: The subject area of FEBS Letters is broad. It covers biochemistry (including protein chemistry, enzymology, nucleic acid chemistry, metabolism, and immunochemistry), structural biology, biophysics, computational biology (genomics, proteomics, bioinformatics), molecular genetics, molecular biology and molecular cell biology (signal transduction, intracellular traffic, regulation of cellular proliferation, cell-cell interactions) and systems biology. Studies on microbes, plants and animals at the molecular level are within the scope of FEBS Letters. Submitting Authors: Manuscripts can be submitted to FEBS Letters at: http://ees.elsevier.com/febsletters/ http://www.febsletters.org//inpress?rss=yesElsevier Inc.en © 2010 Published by Elsevier Inc. FEBS Letters0014-57932010-07-30 © 2010 Published by Elsevier Inc. healthpermissions@elsevier.comhttp://www.febsletters.org/article/PIIS0014579310006046/abstract?rss=yesAbstract: Stem cells regenerate our bodies. In a similar manner to match ignition, stem cell “ignition” has to be precisely tuned to avoid uncontrolled proliferation as may occur in tumors or, inversely, the lack of proliferation as happens in degenerative disorders. During the last years it has become evident that telomeres and telomerase are main components of the stem cell “ignition” mechanism, providing a way to restrain cancer and delay aging.The role of telomeres and telomerase in stem cell aging - Accepted ManuscriptIgnácio Flores, Maria A. Blasco10.1016/j.febslet.2010.07.042FEBS Letters (2010)2010-07-30FEBS Letters2010-07-30REVIEWhttp://www.febsletters.org/article/PIIS0014579310006058/abstract?rss=yesAbstract: The crystal structure of Bifidobacterium longum phosphoketolase, a thiamine diphosphate (TPP) dependent enzyme, has been determined at 2.2 Å resolution. The enzyme is a dimer with the active sites located at the interface between the two identical subunits with molecular mass of 92.5 kDa. The bound TPP is almost completely shielded from solvent except for the catalytically important C2-carbon of the thiazolium ring, which can be accessed by a substrate sugar through a narrow funnel-shaped channel. In silico docking studies of Bifidobacterium longum phosphoketolase with its substrate enable us to propose a model for substrate binding.Structured summary: MINT-7985878:PTK (uniprotkb:Q6R2Q7) and PTK (uniprotkb:Q6R2Q7) bind (MI:0407) by x-ray crystallography (MI:0114)Crystal Structure of Bifidobacterium Longum Phosphoketolase; Key enzyme for Glucose Metabolism in Bifidobacterium - Accepted ManuscriptKazutoshi Takahashi, Uno Tagami, Nobuhisa Shimba, Tatsuki Kashiwagi, Kohki Ishikawa, Ei-ichiro Suzuki10.1016/j.febslet.2010.07.043FEBS Letters (2010)2010-07-30FEBS Letters2010-07-30http://www.febsletters.org/article/PIIS001457931000606X/abstract?rss=yesAbstract: To gain further insight into yeast acetic acid-induced programmed cell death (AA-PCD) we analyzed the effects of the antioxidant N-acetyl-L-cysteine (NAC) on cell viability, hydrogen peroxide (H202) production, DNA fragmentation, cytochrome c (cyt c) release and caspase-like activation in wild type (wt) and metacaspase and/or cyt c-lacking cells. We found that NAC prevents AA-PCD in wt cells, by scavenging H202 and by inhibiting both cyt c release and caspase-like activation. This shows the occurrence of a ROS-dependent AA-PCD. Contrarily no NAC dependent change in AA-PCD of mutant cells was detectable, showing that a ROS-independent AA-PCD can also occur.Knock-out of metacaspase and/or cytochrome c results in the activation of a ROS-independent acetic acid-induced programmed cell death pathway in yeast - Accepted ManuscriptNicoletta Guaragnella, Salvatore Passarella, Ersilia Marra, Sergio Giannattasio10.1016/j.febslet.2010.07.044FEBS Letters (2010)2010-07-30FEBS Letters2010-07-30http://www.febsletters.org/article/PIIS0014579310006083/abstract?rss=yesAbstract: In non-mammalian eukaryotes, an abnormally long 3’ UTR is generally thought to be the definitive signal in the recognition of a premature termination codon (PTC) in nonsense-mediated mRNA decay (NMD). However, because the lengths of 3’ UTRs in normal mRNAs are widely distributed, “abnormally long” is hard to define. Distinct peaks of nucleosome deposition and DNA methylation have recently been found at coding region boundaries. We propose that nucleosomes and DNA methylation just upstream of a normal stop codon are ideal indicators for the position of a normal stop codon and may thus serve as signals in PTC recognition.Nucleosome deposition and DNA methylation may participate in the recognition of premature termination codon in nonsense-mediated mRNA decay - Accepted ManuscriptDeng-Ke Niu, Jian-Li Cao10.1016/j.febslet.2010.07.046FEBS Letters (2010)2010-07-30FEBS Letters2010-07-30HYPOTHESIShttp://www.febsletters.org/article/PIIS0014579310006095/abstract?rss=yesAbstract: Sinorhizobium meliloti is a soil bacterium accumulating glutamate, N-acetylglutaminyl glutamine amide (NAGGN) and trehalose in hyperosmolarity. Besides these compatible solutes, we highlighted several compounds in S. meliloti Rm1021 wild-type strain. The purification and the structural characterization based on LC-ELSD, ESI-HRMS and NMR techniques showed they were four linear oligosaccharides composed of 3, 4, 5 and 6 glucose units all linked by α-(1→2) linkages except a terminal α-(1↔1) linkage. These oligosaccharides were cytoplasmic and were observed in several wild-type strains suggesting they were common features in S. meliloti strains grown in hyperosmolarity.Osmoregulated trehalose-derived oligosaccharides in Sinorhizobium meliloti - Accepted ManuscriptArnaud Brique, Jimi Devassine, Serge Pilard, Dominique Cailleu, Isabelle Gosselin10.1016/j.febslet.2010.07.047FEBS Letters (2010)2010-07-30FEBS Letters2010-07-30http://www.febsletters.org/article/PIIS0014579310006101/abstract?rss=yesAbstract: To investigate the effects of respiration defects on the disease phenotypes, we generated trans-mitochondrial mice (mito-mice) by introducing a mutated G13997A mtDNA, which specifically induces respiratory complex I defects and metastatic potentials in mouse tumor cells. First, we obtained ES cells and chimeric mice containing the G13997A mtDNA, and then we generated mito-mice carrying the G13997A mtDNA via its female germ line transmission. The three-month-old mito-mice showed complex I defects and lactate overproduction, but showed no other phenotypes related to mitochondrial diseases or tumor formation, suggesting that aging or additional nuclear abnormalities are required for expression of other phenotypes.Generation of trans-mitochondrial mito-mice by the introduction of a pathogenic G13997A mtDNA from highly metastatic lung carcinoma cells - Accepted ManuscriptMutsumi Yokota, Hiroshi Shitara, Osamu Hashizume, Kaori Ishikawa, Kazuto Nakada, Rie Ishii, Choji Taya, Keizo Takenaga, Hiromichi Yonekawa, Jun-Ichi Hayashi10.1016/j.febslet.2010.07.048FEBS Letters (2010)2010-07-30FEBS Letters2010-07-30http://www.febsletters.org/article/PIIS0014579310006125/abstract?rss=yesEditorial - Accepted Manuscript10.1016/j.febslet.2010.07.050FEBS Letters (2010)2010-07-30FEBS Letters2010-07-30http://www.febsletters.org/article/PIIS0014579310005995/abstract?rss=yesAbstract: AMP-activated protein kinase (AMPK) plays a pivotal role in regulating cellular energy metabolism. We previously showed that AMPK α1-/- mice develop moderate anemia associated with splenomegaly and high reticulocytosis. Here, we report that splenectomy of AMPK α1-/- mice worsened anemia supporting evidence that AMPK α1 mice developped a compensatory response through extramedullary erythropoiesis in the spleen. Transplantation of bone marrow from AMPK α1-/- mice into wild-type recipients recapitulated the hematologic phenotype. Further, AMPK α1-/- red blood cells (RBC) showed less deformability in response to shear stress limiting their membrane flexibility. Thus, our results highlight the crucial role of AMPK to preserve RBC integrity.Maintenance of red blood cell integrity by AMP-activated protein kinase α1 catalytic subunit - Accepted ManuscriptMarc Foretz, Soizic Guihard, Jocelyne Leclerc, Véronique Fauveau, Jean-Pierre Couty, Fabienne Andris, Murielle Gaudry, Fabrizio Andreelli, Sophie Vaulont, Benoit Viollet10.1016/j.febslet.2010.07.041FEBS Letters (2010)2010-07-27FEBS Letters2010-07-27http://www.febsletters.org/article/PIIS0014579310005922/abstract?rss=yesAbstract: The role of transcription factor activator protein-2β (AP-2β) in foam cell formation was investigated. Uptake assay of DiI-labeled oxidized low density lipoprotein and the lipid quantitative analysis by high performance liquid chromatography showed AP-2β promoted the lipid accumulation. The quantitative real-time RT-PCR and Western blot indicated that AP-2β upregulated the expression of CD36. Luciferase assay, electrophoretic mobility shift assay and chromatin immunoprecipitation confirmed that AP-2β bound to AP-2 binding sites in CD36 promoter region and enhanced the promoter activity of CD36 gene. We conclude that AP-2β may function in foam cell formation through enhancing the transcription and expression of CD36 followed by increased lipid uptake.Transcription factor activator protein-2β accelerates lipid accumulation in macrophages via enhancing the transcription of CD36 - Uncorrected ProofLu Gan, Dongxing Zhu, Zhenhua Ding10.1016/j.febslet.2010.07.034FEBS Letters (2010)2010-07-26FEBS Letters2010-07-26http://www.febsletters.org/article/PIIS0014579310005934/abstract?rss=yesAbstract: Ezetimibe stimulates faecal neutral sterol (FNS) excretion in mice, which cannot be explained by cholesterol absorption inhibition alone. We investigated whether these effects are mediated via the sterol exporter ATP binding cassette transporter G8 (abcg8). Ezetimibe increased FNS excretion 2.7-fold in WT mice and 1.5-fold in abcg8−/− mice, without affecting biliary cholesterol secretion. Daily FNS excretion exceeded the sum of dietary cholesterol intake and biliary secretion by about 60%. Ezetimibe enhanced this ‘extra’ FNS excretion by 3.5-fold and 1.5-fold in wildtype (WT) and abcg8−/− mice, respectively. Ezetimibe stimulates fecal sterol excretion of non-biliary and non-dietary origin, probably through stimulation of trans-intestinal cholesterol excretion. We show that this effect depends on intact abcg8 function.Ezetimibe stimulates faecal neutral sterol excretion depending on abcg8 function in mice - Uncorrected ProofLily Jakulj, Maud N. Vissers, Cindy P. van Roomen, Jelske N. van der Veen, Carlos L.J. Vrins, Cindy Kunne, Frans Stellaard, John J.P. Kastelein, Albert K. Groen10.1016/j.febslet.2010.07.035FEBS Letters (2010)2010-07-26FEBS Letters2010-07-26http://www.febsletters.org/article/PIIS0014579310005946/abstract?rss=yesAbstract: Recombinant expression of eukaryotic proteins in bacteria often results in misfolding and aggregation. The ribosome-binding Trigger factor (TF) is the first molecular chaperone that interacts with nascent polypeptide chains in bacteria. Here we show that mutant TF lacking the PPIase domain (TFNC) is more efficient than wild-type TF in enhancing the folding yield of multi-domain proteins such as firefly luciferase. We find that TFNC has a shorter residence time on nascent chains, thus facilitating co-translational folding. By delaying folding relative to translation, the PPIase domain may increase the propensity of misfolding for certain eukaryotic proteins that rely on a mechanism of co-translational, domain-wise folding.Trigger factor lacking the PPIase domain can enhance the folding of eukaryotic multi-domain proteins in Escherichia coli - Uncorrected ProofRashmi Gupta, Sathish Kumar Lakshmipathy, Hung-Chun Chang, Stephanie A. Etchells, F. Ulrich Hartl10.1016/j.febslet.2010.07.036FEBS Letters (2010)2010-07-26FEBS Letters2010-07-26http://www.febsletters.org/article/PIIS0014579310005958/abstract?rss=yesAbstract: Nobox is an oocyte-specific transcriptional regulator. Nobox deficiency disrupts early folliculogenesis and the expression of oocyte-specific genes in mice. In the present study, we found that peptidylarginine deiminase 6 (Pad6) was downregulated in Nobox-null ovaries. Pad6 is preferentially expressed in oocytes and its transcript is detectable at embryonic day 16.5. In addition, we identified one Nobox DNA-binding element (NBE) within the mouse Pad6 promoter. The NBE includes a core sequence TAATTA. Sequence-specific binding of Nobox to the TAATTA motif was confirmed. Nobox overexpression augmented transcriptional activity of a luciferase reporter driven by mouse Pad6. Our findings indicate that Nobox is a critical regulator that orchestrates oocyte-specific genes such as Pad6 during folliculogenesis.The oocyte-specific transcription factor, Nobox, regulates the expression of Pad6, a peptidylarginine deiminase in the oocyte - Uncorrected ProofMikyung Choi, Ok-Hee Lee, Sanghyun Jeon, Miseon Park, Dong-Ryul Lee, Jeong-Jae Ko, Tae Ki Yoon, Aleksandar Rajkovic, Youngsok Choi10.1016/j.febslet.2010.07.037FEBS Letters (2010)2010-07-26FEBS Letters2010-07-26http://www.febsletters.org/article/PIIS001457931000596X/abstract?rss=yesAbstract: Currently, some efforts have been devoted to the text analysis of disease phenotype data, and their results indicated that similar disease phenotypes arise from functionally related genes. These related genes work together, as a functional module, to perform a desired cellular function. We constructed a text-based human disease phenotype network and detected 82 disease-specific gene functional modules, each corresponding to a different phenotype cluster, by means of graph-based clustering and mapping from disease phenotype to gene. Since genes in such gene functional modules are functionally related and cause clinically similar diseases, they may share common genetic origin of their associated disease phenotypes. We believe the investigation may facilitate the ultimate understanding of the common pathophysiologic basis of associated diseases.From phenotype to gene: Detecting disease-specific gene functional modules via a text-based human disease phenotype network construction - Uncorrected ProofShi-Hua Zhang, Chao Wu, Xia Li, Xi Chen, Wei Jiang, Bin-Sheng Gong, Jiang Li, Yu-Qing Yan10.1016/j.febslet.2010.07.038FEBS Letters (2010)2010-07-26FEBS Letters2010-07-26http://www.febsletters.org/article/PIIS0014579310005971/abstract?rss=yesAbstract: The twin-arginine translocation (Tat) system translocates folded proteins across biological membranes. It has beensuggested that the Tat system of Escherichia coli can direct Tat substrates to degradation if they are not properly folded [Matos, C.F., Robinson, C. and Di Cola, A. (2008) The Tat system proofreads FeS protein substrates and directly initiates the disposal of rejected molecules. EMBO J. 27, 2055–2063; Matos, C.F., Di Cola, A. and Robinson, C. (2009) TatD is a central component of a Tat translocon-initiated quality control system for exported FeS proteins in Escherichia coli. EMBO Rep. 10, 474–479]. Contrary to the earlier reports, it is now concluded that reported differences between tested strains were due to variations in expression levels and inclusion body formation. Using the native Tat substrate NrfC and a malfolded variant thereof, we show that the turnover of these proteins is not affected by the absence of all known Tat components. Malfolded NrfC is degraded more quickly than the native protein, indicating that Tat-independent protease systems can recognize malfolded Tat substrates.Malfolded recombinant Tat substrates are Tat-independently degraded in Escherichia coli - Uncorrected ProofUte Lindenstrauß, Cristina Matos, Wenke Graubner, Colin Robinson, Thomas Brüser10.1016/j.febslet.2010.07.039FEBS Letters (2010)2010-07-26FEBS Letters2010-07-26http://www.febsletters.org/article/PIIS0014579310005983/abstract?rss=yesAbstract: The effect of insulin on endoplasmic reticulum (ER) stress was investigated. Insulin protected cell death induced by ER stress and increased glucose-regulated protein 78 (GRP78) mRNA and protein levels. Insulin also significantly increased activating transcription factor-4 (ATF4) protein in the nucleus, which was inhibited by LY294002, a phosphatidylinositol 3-kinase (PI-3 kinase) inhibitor. The increase of ATF4 protein by insulin was not due to transcriptional or translational up-regulation but to a post-translational mechanism. Knockdown of ATF4 by siRNA significantly inhibited GRP78 induction by insulin. These results indicate that insulin modulated ER stress-induced GRP78 expression occurs via ATF4 up-regulation.Insulin modulates induction of glucose-regulated protein 78 during endoplasmic reticulum stress via augmentation of ATF4 expression in human neuroblastoma cells - Accepted ManuscriptKiyoshi Inageda10.1016/j.febslet.2010.07.040FEBS Letters (2010)2010-07-26FEBS Letters2010-07-26http://www.febsletters.org/article/PIIS0014579310005892/abstract?rss=yesAbstract: In this review we present critical overview of some of the available literature on the fundamental biology of telomeres and telomerase in Metazoan. With the exception of Nematodes and Arthropods, the (TTAGGG)n sequence is conserved in most Metazoa. Available data show that telomerase-based end maintenance is a very ancient mechanism in unicellular and multicellular organisms. In invertebrates, fish, amphibian, and reptiles persistent telomerase activity in somatic tissues might allow the maintenance of the extensive regenerative potentials of these species. Telomerase repression among birds and many mammals suggests that, as humans, they may use replicative aging as a tumor protection mechanism.Telomere biology in Metazoa - Uncorrected ProofNuno M.V. Gomes, Jerry W. Shay, Woodring E. Wright10.1016/j.febslet.2010.07.031FEBS Letters (2010)2010-07-23FEBS Letters2010-07-23REVIEWhttp://www.febsletters.org/article/PIIS0014579310005909/abstract?rss=yesAbstract: Telomeres are heterochromatic structures at the ends of eukaryotic chromosomes. As other heterochromatin regions, telomeres are transcribed from the subtelomeric region towards chromosome ends into the long non-coding RNA TERRA. Telomere transcription is a widespread phenomenon as it has been observed in species belonging to several kingdoms of the eukaryotic domain. TERRA is part of telomeric heterochromatin in addition to being present in the nucleoplasm. Here, we review the current knowledge of TERRA structure, biogenesis and turnover. In addition, we discuss presumed roles of this RNA during replication of telomeric DNA, heterochromatin formation and the regulation of telomerase.TERRA biogenesis, turnover and implications for function - Uncorrected ProofSascha Feuerhahn, Nahid Iglesias, Andrea Panza, Antonio Porro, Joachim Lingner10.1016/j.febslet.2010.07.032FEBS Letters (2010)2010-07-23FEBS Letters2010-07-23REVIEWhttp://www.febsletters.org/article/PIIS0014579310005910/abstract?rss=yesAbstract: Methionine sulfoxide reductase A (msrA) was previously found to increase resistance to oxidative stress and longevity in animals. We identified Drosophila msrA (dmsrA), a Drosophila homolog of human msrA, as a downstream effector of forkhead box O (FOXO) signaling in Drosophila, which enhances resistance to oxidative stress and increases survival under stressed conditions. Additionally, overexpression of dmsrA in neurons extended the lifespan of flies. Moreover, overexpression of dmsrA in fat body cells caused FOXO to translocate to the nucleus, implying that this possible positive feedback loop between dmsrA and FOXO could potentiate the antioxidant activity of dmsrA and increase the lifespan in Drosophila.The Drosophila homolog of methionine sulfoxide reductase A extends lifespan and increases nuclear localization of FOXO - Uncorrected ProofHyewon Chung, Ae kyeong Kim, Sun-Ah Jung, Si Wouk Kim, Kweon Yu, Joon H. Lee10.1016/j.febslet.2010.07.033FEBS Letters (2010)2010-07-23FEBS Letters2010-07-23http://www.febsletters.org/article/PIIS0014579310005855/abstract?rss=yesAbstract: Hsp60 is an important component of defense mechanisms against diabetic myocardial injury; however, the cause of Hsp60 reduction in the diabetic myocardium remains unknown. After stimulation of cardiomyocytes with high glucose in vivo and in vitro, significant up-regulation of miR-1/miR-206 and post-transcriptional modulation of Hsp 60 were observed. Serum response factor (SRF) and the MEK1/2 pathway were involved in miR-1 and miR-206 expression in cardiomyocytes. miR-1 and miR-206 regulated Hsp60 expression post-transcriptionally and accelerated cardiomyocyte apoptosis through Hsp60. These results revealed that miR-1 and miR-206 regulate Hsp60 expression, contributing to high glucose-mediated apoptosis in cardiomyocytes.miR-1/miR-206 regulate Hsp60 expression contributing to glucose-mediated apoptosis in cardiomyocytes - Uncorrected ProofZhi-Xin Shan, Qiu-Xiong Lin, Chun-Yu Deng, Jie-Ning Zhu, Li-Ping Mai, Ju-Li Liu, Yong-Heng Fu, Xiao-Ying Liu, Yang-Xin Li, You-Yi Zhang, Shu-Guang Lin, Xi-Yong Yu10.1016/j.febslet.2010.07.027FEBS Letters (2010)2010-07-22FEBS Letters2010-07-22http://www.febsletters.org/article/PIIS0014579310005867/abstract?rss=yesAbstract: In this study, we found that expression and secretion of galectin-3 (GAL-3) were upregulated by amyloid-β42 (Aβ42) exposure in human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSC) without cell death. Aβ42-exposed rat primary cortical neuronal cells co-treated with recombinant GAL-3 were protected from neuronal death in a dose-dependent manner. hUCB-MSCs were cocultured with Aβ42-exposed rat primary neuronal cells or the neuroblastoma cell line SH-SY5Y in a Transwell chamber. Coculture of hUCB-MSCs reduced cell death of Aβ42-exposed neurons and SH-SY5Y cells. This neuroprotective effect of hUCB-MSCs was reduced significantly by GAL-3 siRNA. These data suggested that hUCB-MSC-derived GAL-3 is a survival factor against Aβ42 neurotoxicity.Galectin-3 secreted by human umbilical cord blood-derived mesenchymal stem cells reduces amyloid-β42 neurotoxicity in vitro - Uncorrected ProofJu-Yeon Kim, Dong Hyun Kim, Dal-Soo Kim, Ji Hyun Kim, Sang Young Jeong, Hong Bae Jeon, Eun Hui Lee, Yoon Sun Yang, Wonil Oh, Jong Wook Chang10.1016/j.febslet.2010.07.028FEBS Letters (2010)2010-07-22FEBS Letters2010-07-22http://www.febsletters.org/article/PIIS0014579310005879/abstract?rss=yesAbstract: Genomes are subject to constant threat by damaging agents that generate DNA double-strand breaks (DSBs). The ends of linear chromosomes need to be protected from DNA damage recognition and end-joining, and this is achieved through protein–DNA complexes known as telomeres. The Mre11–Rad50–Nbs1 (MRN) complex plays important roles in detection and signaling of DSBs, as well as the repair pathways of homologous recombination (HR) and non-homologous end-joining (NHEJ). In addition, MRN associates with telomeres and contributes to their maintenance. Here, we provide an overview of MRN functions at DSBs, and examine its roles in telomere maintenance and dysfunction.The MRN complex in double-strand break repair and telomere maintenance - Uncorrected ProofBrandon J. Lamarche, Nicole I. Orazio, Matthew D. Weitzman10.1016/j.febslet.2010.07.029FEBS Letters (2010)2010-07-22FEBS Letters2010-07-22REVIEWhttp://www.febsletters.org/article/PIIS0014579310005880/abstract?rss=yesThis special issue features in-depth reviews of telomere biology and DNA repair. Understanding how telomeres function requires insights into the nature and regulation of the cellular pathways that detect and repair DNA lesions. As telomeres block unwarranted DNA repair reactions and avoid detection by the DNA damage signaling pathways, detailed knowledge of the earliest steps in the relevant DNA damage response pathways can point to the possible regulatory nodes where telomeres interfere with these processes. Furthermore, telomeres have co-opted some of the complexes involved in the DNA damage response, presumably to serve specific protective roles or facilitate the maintenance of the telomeric DNA. Conversely, studies of dysfunctional telomeres have shed new light on the regulation and nature of the cellular DNA damage response, illuminating specific attributes of the pathways that are not readily apparent from the analysis of genome-wide DNA damage. This cross-fertilization between the two fields is reminiscent of how immunologists have furthered the understanding of pathogens and, vice versa, how virologists and microbiologists have provided insights into the host defense system. It is anticipated that efforts like this special issue will foster a continued interdisciplinary synergy between the DNA repair and telomere biology fields.Telomere biology and DNA repair: Enemies with benefits - Uncorrected ProofTitia de Lange10.1016/j.febslet.2010.07.030FEBS Letters (2010)2010-07-22FEBS Letters2010-07-22PREFACEhttp://www.febsletters.org/article/PIIS0014579310005326/abstract?rss=yesAbstract: l-Xylulose reductase is part of the eukaryotic pathway for l-arabinose catabolism. A previously identified l-xylulose reductase in Hypocrea jecorina turned out to be not the ‘true’ one since it was not upregulated during growth on l-arabinose and the deletion strain showed no reduced l-xylulose reductase activity but instead lost the d-mannitol dehydrogenase activity . In this communication we identified the ‘true’ l-xylulose reductase in Aspergillus niger. The gene, lxrA (JGI177736), is upregulated on l-arabinose and the deletion results in a strain lacking the NADPH-specific l-xylulose reductase activity and having reduced growth on l-arabinose. The purified enzyme had a Km for l-xylulose of 25mM and a νmax of 650U/mg.The ‘true’ l-xylulose reductase of filamentous fungi identified in Aspergillus niger - Uncorrected ProofDominik Mojzita, Kiira Vuoristo, Outi M. Koivistoinen, Merja Penttilä, Peter Richard10.1016/j.febslet.2010.06.037FEBS Letters (2010)2010-07-21FEBS Letters2010-07-21http://www.febsletters.org/article/PIIS0014579310005788/abstract?rss=yesAbstract: The identity of the histidine specific transfer RNA (tRNAHis) is largely determined by a unique guanosine residue at position −1. In eukaryotes and archaea, the tRNAHis guanylyltransferase (Thg1) catalyzes 3′–5′ addition of G to the 5′-terminus of tRNAHis. Here, we show that Thg1 also occurs in bacteria. We demonstrate in vitro Thg1 activity for recombinant enzymes from the two bacteria Bacillus thuringiensis and Myxococcus xanthus and provide a closer investigation of several archaeal Thg1. The reaction mechanism of prokaryotic Thg1 differs from eukaryotic enzymes, as it does not require ATP. Complementation of a yeast thg1 knockout strain with bacterial Thg1 verified in vivo activity and suggests a relaxed recognition of the discriminator base in bacteria.3′–5′ tRNAHis guanylyltransferase in bacteria - Uncorrected ProofIlka Heinemann, Lennart Randau, Robert J. Tomko, Dieter Söll10.1016/j.febslet.2010.07.023FEBS Letters (2010)2010-07-20FEBS Letters2010-07-20http://www.febsletters.org/article/PIIS001457931000579X/abstract?rss=yesAbstract: The inhibitors to plastid gene expression (PGE) were effective in preventing nuclear photosynthetic gene expression only if applied within the first 2–3days of Arabidopsis seedling development. However, the signal transduction processes are still unknown. In this investigation, we found 3% glucose with 1mM chloramphenicol co-treatment repressed LHCB transcript significantly in mature Arabidopsis seedlings, while effective solo glucose treatment needed a concentration of 7%. The repressive effects of glucose and chloramphenicol on LHCB expression were inhibited in phxk (plastid hexokinase) mutant. pHXK enzyme activities, location, function in signal transduction, and cross talk to plastid GUN1 protein (a key signaling factor) were also investigated. The data suggest that pHXK may be a node of convergence for sugar-mediated and PGE-derived signals in Arabidopsis.The plastid hexokinase pHXK: A node of convergence for sugar and plastid signals in Arabidopsis - Corrected ProofZhong-Wei Zhang, Shu Yuan, Fei Xu, Hui Yang, Nian-Hui Zhang, Jian Cheng, Hong-Hui Lin10.1016/j.febslet.2010.07.024FEBS Letters (2010)2010-07-20FEBS Letters2010-07-20http://www.febsletters.org/article/PIIS0014579310005818/abstract?rss=yesAbstract: Treatment of Caenorhabditis elegans with apigenin, 5,7,4′-trihydroxyflavone, induces larval growth inhibition. To understand the molecular basis of apigenin-induced larval growth inhibition, the effects of apigenin on DAF-16 activity were examined. DAF-16 was activated through nuclear translocation and the mRNA level of sod-3, one of the known DAF-16 target genes, was increased upon apigenin treatment. DAF-16 activity was required for the growth inhibition, since the larval growth retardation upon apigenin treatment was suppressed in daf-16 mutants. These results indicate that apigenin acts as a stressor that activates DAF-16, which in turn inhibits larval growth.Apigenin inhibits larval growth of Caenorhabditis elegans through DAF-16 activation - Corrected ProofIchiro Kawasaki, Myung-Hwan Jeong, Bong-Kyeong Oh, Yhong-Hee Shim10.1016/j.febslet.2010.07.026FEBS Letters (2010)2010-07-20FEBS Letters2010-07-20http://www.febsletters.org/article/PIIS0014579310005764/abstract?rss=yesAbstract: For the GalNAcα1→ specific Agaricus bisporus agglutinin (ABA) from an edible mushroom, the mechanism of polyvalent Galβ1→3/4GlcNAcβ1→ complex in ABA–carbohydrate recognition has not been well defined since Gal and GlcNAc are weak ligands. By enzyme-linked lectinosorbent and inhibition assays, we show that the polyvalent Galβ1→3/4GlcNAcβ1→ in natural glycans also play vital roles in binding and we propose that four different intensities of glycotopes (Galβ1-3GalNAcα1-, GalNAcα1-Ser/Thr and Galβ1-3/4GlcNAcβ1-) construct three recognition systems at the same domain. This peculiar concept provides the most comprehensive mechanism for the attachment of ABA to target glycans and malignant cells at the molecular level.Multiple recognition systems adopting four different glycotopes at the same domain for the Agaricus bisporus agglutinin–glycan interactions - Corrected ProofAlbert M. Wu, Jia-Hau Liu, Yu-Ping Gong, Chia-Chen Li, En-Tzu Chang10.1016/j.febslet.2010.07.021FEBS Letters (2010)2010-07-19FEBS Letters2010-07-19http://www.febsletters.org/article/PIIS0014579310005776/abstract?rss=yesAbstract: SGs are mRNA containing cytoplasmic structures that are assembled in response to stress. Tudor-SN protein is a ubiquitously expressed protein. Here, Tudor-SN protein was found to physiologically interact with G3BP, which is the marker and effector of SG. The kinetics of the assembly of SGs in the living cells demonstrated that Tudor-SN co-localizes with G3BP and is recruited to the same SGs in response to different stress stimuli. Knockdown of endogenous Tudor-SN did not inhibit the formation of SGs, but retarded the aggregation of small SGs into large SGs. Thus Tudor-SN may not be an initiator as essential as G3BP for the formation of SGs, but affects the aggregation of SGs. These findings identify Tudor-SN as a novel component of SGs.Structured summary: MINT-7968768, MINT-7968779: Tudor-SN (uniprotkb:Q7KZF4) physically interacts (MI:0915) with G3BP (uniprotkb:Q13283) by anti bait coimmunoprecipitation (MI:0006) MINT-7968800: Tudor-SN (uniprotkb:Q7KZF4) and TIA-1 (uniprotkb:P31483) colocalize (MI:0403) by fluorescence microscopy (MI:0416) MINT-7968789: Tudor-SN (uniprotkb:Q7KZF4) and G3BP (uniprotkb:Q13283) colocalize (MI:0403) by fluorescence microscopy (MI:0416)Tudor-SN interacts with and co-localizes with G3BP in stress granules under stress conditions - Corrected ProofXingjie Gao, Lin Ge, Jie Shao, Chao Su, Hong Zhao, Juha Saarikettu, Xuyang Yao, Zhi Yao, Olli Silvennoinen, Jie Yang10.1016/j.febslet.2010.07.022FEBS Letters (2010)2010-07-19FEBS Letters2010-07-19http://www.febsletters.org/article/PIIS0014579310005806/abstract?rss=yesAbstract: Prolonged (12h) exposure of SH-SY5Y neuroblastoma cells to the mu-opioid receptor (MOPr) agonist [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) causes homologous desensitization as well as heterologous desensitization of the extracellular signal-regulated kinase 1/2 (ERK 1/2) phosphorylation induced by insulin-like growth factor (IGF)-I. Brief (15min) but not prolonged exposure to DAMGO transregulates the insulin-like growth factor-I (IGF-I) receptor, as evidenced by its phosphorylation in the absence of IGF-I. Silencing of β-arrestin 2 uncouples the crosstalk between the two receptors, thus maintaining IGF-I-mediated receptor phosphorylation and ERK 1/2 activation even after prolonged DAMGO exposure. Furthermore, MOPr-induced activation of IGF-I receptor requires the tyrosine kinase c-Src.β-Arrestin 2-mediated heterologous desensitization of IGF-IR by prolonged exposure of SH-SY5Y neuroblastoma cells to a mu opioid agonist - Corrected ProofAntonino Spartà, Monica Baiula, Gayle Campbell, Santi Spampinato10.1016/j.febslet.2010.07.025FEBS Letters (2010)2010-07-19FEBS Letters2010-07-19http://www.febsletters.org/article/PIIS0014579310005715/abstract?rss=yesAbstract: Retrovirus replication critically depends on a dynamic interplay between retroviral and host proteins. We report on the binding of the surface subunit (glycoprotein 120 (gp120)) of the human immunodeficiency virus type 1 (HIV-1) envelope protein (Env) to the cytoplasmic C-terminus of the voltage-gated potassium channel BEC1 (brain-specific ether-a-go-go-like channel 1), an interaction that can result in the repression of BEC’s activity and the inhibition of HIV-1 particle-release. BEC1 protein was found to be expressed in T cells and macrophages, the major target cells of HIV-1. Thus, gp120/BEC1 interaction may be involved in HIV-1 life cycle and/or pathogenesis.Structured summary: MINT-7968695: BEC1 (uniprotkb:Q9ULD8) physically interacts (MI:0915) with gp160 (uniprotkb:P04578) by anti bait coimmunoprecipitation (MI:0006)MINT-7968714: BEC1 (uniprotkb:Q9ULD8) physically interacts (MI:0915) with gp160 (uniprotkb:P04578) by anti tag coimmunoprecipitation (MI:0007)MINT-7968675: BEC1 (uniprotkb:Q9ULD8) physically interacts (MI:0915) with gp160 (uniprotkb:P04578) by pull down (MI:0096)Interaction of human immunodeficiency virus gp120 with the voltage-gated potassium channel BEC1 - Corrected ProofMadeleine Herrmann, Klemens Ruprecht, Marlies Sauter, Javier Martinez, Pearl van Heteren, Michael Glas, Barbara Best, Andreas Meyerhans, Klaus Roemer, Nikolaus Mueller-Lantzsch10.1016/j.febslet.2010.07.016FEBS Letters (2010)2010-07-16FEBS Letters2010-07-16http://www.febsletters.org/article/PIIS0014579310005727/abstract?rss=yesAbstract: Microtubules are composed of polymerized α/β-tubulin heterodimers. Biogenesis of assembly-competent tubulin dimers is a complex multistep process that requires sequential actions of distinct molecular chaperones and cofactors. Tubulin folding cofactor A (TFCA), which captures β-tubulin during the folding pathway, has been identified in many organisms. Here, we report the crystal structure of Arabidopsis thaliana TFC A (KIESEL, KIS), which forms a monomeric three-helix bundle. The functional binding analysis demonstrated that KIS interacts with β-tubulin in plant. Furthermore, mutagenesis studies indicated that the α-helical regions of KIS participate in β-tubulin binding. Unlike the budding yeast TFC A, the two loop regions of KIS are not required for this interaction suggesting a distinct binding mechanism of TFC A to β-tubulin in plants.Structured summary: MINT-7968902, MINT-7968915, MINT-7968951, MINT-7968966: KIS (uniprotkb:O04350) physically interacts (MI:0915) with Tub9 (uniprotkb:P29517) by anti tag coimmunoprecipitation (MI:0007)MINT-7968928: KIS (uniprotkb:O04350) and Tub9 (uniprotkb:P29517) physically interact (MI:0915) by bimolecular fluorescence complementation (MI:0809)Crystal structure of tubulin folding cofactor A from Arabidopsis thaliana and its β-tubulin binding characterization - Corrected ProofLu Lu, Jie Nan, Wei Mi, Lan-Fen Li, Chun-Hong Wei, Xiao-Dong Su, Yi Li10.1016/j.febslet.2010.07.017FEBS Letters (2010)2010-07-16FEBS Letters2010-07-16http://www.febsletters.org/article/PIIS0014579310005739/abstract?rss=yesAbstract: We reported a novel interaction between Beclin 1, a key regulator of autophagy, and survivin, a member of the inhibitor of apoptosis protein family. We found that knock-down of Beclin 1 down-regulated survivin protein, and the turnover rate of survivin was increased when Beclin 1 expression was silenced. Knock-down of Beclin 1 sensitized glioma cells to TRAIL-induced apoptosis, and introduction of survivin antagonized the sensitizing effect, suggesting that down-regulation of survivin mediates the enhanced sensitivity to TRAIL-induced apoptosis. These results demonstrate a novel interaction between Beclin 1 and survivin, and may provide a potential mechanism underlying the cross-talk between autophagy and apoptosis.Structured summary: MINT-7969366: Beclin-1 (uniprotkb:Q14457) physically interacts (MI:0915) with survivin (uniprotkb:O15392) by anti tag coimmunoprecipitation (MI:0007)MINT-7968986, MINT-7969161: survivin (uniprotkb:O15392) physically interacts (MI:0915) with Beclin-1 (uniprotkb:Q14457) by anti bait coimmunoprecipitation (MI:0006)Interaction of Beclin 1 with survivin regulates sensitivity of human glioma cells to TRAIL-induced apoptosis - Corrected ProofTing-Kuang Niu, Yan Cheng, Xingcong Ren, Jin-Ming Yang10.1016/j.febslet.2010.07.018FEBS Letters (2010)2010-07-16FEBS Letters2010-07-16http://www.febsletters.org/article/PIIS0014579310005752/abstract?rss=yesAbstract: During Drosophila embryogenesis, establishment of ventral and lateral cell fates requires spatial regulation of an extracellular serine protease cascade composed of Nudel, Gastrulation Defective (GD), Snake, and Easter. Pipe, a sulfotransferase expressed ventrally during oogenesis, sulfates secreted targets that somehow confer positive spatial input to this cascade. Nudel and GD activation are pipe-independent, while Easter activation requires pipe. The effect of pipe on Snake activation has been unknown. Here we show that Snake activation is cascade-dependent but pipe-independent. These findings support a conclusion that Snake’s activation of Easter is the first spatially regulated step in the dorsoventral protease cascade.Activation of Snake in a serine protease cascade that defines the dorsoventral axis is atypical and pipe-independent in Drosophila embryos - Corrected ProofPamela W. Steen, Sufang Tian, Sarah E. Tully, Benjamin F. Cravatt, Ellen K. LeMosy10.1016/j.febslet.2010.07.020FEBS Letters (2010)2010-07-16FEBS Letters2010-07-16http://www.febsletters.org/article/PIIS0014579310005612/abstract?rss=yesAbstract: Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expressed in Saccharomyces cerevisiae was reversibly oxidized by hydrogen peroxide and reduced by cellular reductants. Reduction of hPTEN was delayed in each of S. cerevisiae gsh1Δ and gsh2Δ mutants. Expression of γ-glutamylcysteine synthetase Gsh1 in the gsh1Δ mutant rescued regeneration rate of hPTEN. Oxidized hPTEN was reduced by glutathione in a concentration- and time-dependent manner. Glutathionylated PTEN was detected. Incubation of 293T cells with BSO and knockdown expression of GCLc in HeLa cells by siRNA resulted in the delay of reduction of oxidized PTEN. Also, in HeLa cells transfected with GCLc siRNA, stimulation with epidermal growth factor resulted in the increase of oxidized PTEN and phosphorylation of Akt. These results suggest that the reduction of oxidized hPTEN is mediated by glutathione.Redox regulation of the tumor suppressor PTEN by glutathione - Corrected ProofYujeong Kim, Yong Bhum Song, Tae-Youl Kim, Inyoung Kim, Seong-Jeong Han, Younghee Ahn, Seung-Hyun Cho, Cheol Yong Choi, Kee-Oh Chay, Sung Yeul Yang, Bong Whan Ahn, Won-Ki Huh, Seung-Rock Lee10.1016/j.febslet.2010.07.006FEBS Letters (2010)2010-07-14FEBS Letters2010-07-14http://www.febsletters.org/article/PIIS0014579310005624/abstract?rss=yesAbstract: Telomeres protect the ends of eukaryotic chromosomes from being recognized and processed as double strand breaks. In most organisms, telomeric DNA is highly repetitive with a high GC-content. Moreover, the G residues are concentrated in the strand running 3′–5′ from the end of the chromosome towards its center. This G-rich strand is extended to form a 3′ single-stranded tail that can form unusual secondary structures such as T-loops and G-quadruplex DNA. Both the duplex repeats and the single-stranded G-tail are assembled into stable protein–DNA complexes. The unique architecture, high GC content, and multi-protein association create particularly stable protein–DNA complexes that are a challenge for replication, recombination, and transcription. Helicases utilize the energy of nucleotide hydrolysis to unwind base paired nucleic acids and, in some cases, to displace proteins from them. The telomeric functions of helicases from the RecQ, Pifl, FANCJ, and DNA2 families are reviewed in this article. We summarize data showing that perturbation of their telomere activities can lead to telomere dysfunction and genome instability and in some cases human disease.Telomeres: Structures in need of unwinding - Corrected ProofKatrin Paeschke, Karin R. McDonald, Virginia A. Zakian10.1016/j.febslet.2010.07.007FEBS Letters (2010)2010-07-14FEBS Letters2010-07-14REVIEWhttp://www.febsletters.org/article/PIIS0014579310005582/abstract?rss=yesAbstract: In this study, we demonstrated that human type-5 adenovirus infected the brain of the teleost fish, medaka (Oryzias latipes), in vivo. Injection of adenovirus vector into the mesencephalic ventricle of medaka larvae induced the expression of reporter genes in some parts of the telencephalon, the periventricular area of the mesencephalon and diencephalon, and the cerebellum. Additionally, the Cre-loxP system works in medaka brains using transgenic medaka carrying a vector containing DsRed2, flanked by loxP sites under control of the β-actin promoter and downstream promoterless enhanced green fluorescent protein (EGFP). We demonstrated that the presence of green fluorescence depended on injection of adenovirus vector expressing the Cre gene and confirmed that EGFP mRNA was transcribed in the virus-injected larvae.Transient and permanent gene transfer into the brain of the teleost fish medaka (Oryzias latipes) using human adenovirus and the Cre-loxP system - Uncorrected ProofYuji Suehiro, Masato Kinoshita, Teruhiro Okuyama, Atsuko Shimada, Kiyoshi Naruse, Hiroyuki Takeda, Takeo Kubo, Mitsuhiro Hashimoto, Hideaki Takeuchi10.1016/j.febslet.2010.06.047FEBS Letters (2010)2010-07-09FEBS Letters2010-07-09http://www.febsletters.org/article/PIIS0014579310005260/abstract?rss=yesAbstract: Telomeres protect the ends of linear chromosomes from activities that cause sequence losses or challenge chromosome integrity. Furthermore, these ends must be hidden from detection by the DNA damage recognition and response pathways. In particular, they must not fuse with each other. These fundamental and very first functions attributed to telomeres are also summarized with the term ‘chromosome capping’. However, telomeres can become uncapped and the foremost cellular responses to such events aim to restore genome stability in the most conservative fashion possible. I will provide an outline of cellular responses to uncapping in budding yeast and briefly discuss the reverse, namely avoidance mechanisms that prevent telomere formation at inappropriate places.When the caps fall off: Responses to telomere uncapping in yeast - Corrected ProofRaymund J. Wellinger10.1016/j.febslet.2010.06.031FEBS Letters (2010)2010-06-25FEBS Letters2010-06-25REVIEWhttp://www.febsletters.org/article/PIIS0014579310005065/abstract?rss=yesAbstract: The linear nature of eukaryotic chromosomes leaves natural DNA ends susceptible to triggering DNA damage responses. Telomeres are specialized nucleoprotein structures that comprise the “end zone” of chromosomes. Besides having specialized sequences and structures, there are six resident proteins at telomeres that play prominent roles in protecting chromosome ends. In this review, we discuss this team of proteins, termed shelterin, and how it is involved in regulating DNA damage signaling, repair and replication at telomeres.Defending the end zone: Studying the players involved in protecting chromosome ends - Corrected ProofSuzanne S. Chan, Sandy Chang10.1016/j.febslet.2010.06.016FEBS Letters (2010)2010-06-18FEBS Letters2010-06-18REVIEWhttp://www.febsletters.org/article/PIIS0014579310005077/abstract?rss=yesAbstract: Telomeres are essential structures at the ends of eukaryotic chromosomes. Work on their structure and function began almost 70 years ago in plants and flies, continued through the Nobel Prize winning work on yeast and ciliates, and goes on today in many model and non-model organisms. The basic molecular mechanisms of telomeres are highly conserved throughout evolution, and our current understanding of how telomeres function is a conglomeration of insights gained from many different species. This review will compare the current knowledge of telomeres in plants with other organisms, with special focus on the functional length of telomeric DNA, the search for TRF homologs, the family of POT1 proteins, and the recent discovery of members of the CST complex.Comparative biology of telomeres: Where plants stand - Corrected ProofJ. Matthew Watson, Karel Riha10.1016/j.febslet.2010.06.017FEBS Letters (2010)2010-06-18FEBS Letters2010-06-18REVIEWhttp://www.febsletters.org/article/PIIS0014579310004904/abstract?rss=yesAbstract: Alternative Lengthening of Telomeres (ALT) activity can be deduced from the presence of telomere length maintenance in the absence of telomerase activity. More convenient assays for ALT utilize phenotypic markers of ALT activity, but only a few of these assays are potentially definitive. Here we assess each of the current ALT assays and their implications for understanding the ALT mechanism. We also review the clinical situations where availability of an ALT activity assay would be advantageous. The prevalence of ALT ranges from 25% to 60% in sarcomas and 5% to 15% in carcinomas. Patients with many of these types of ALT[+] tumors have a poor prognosis.Assaying and investigating Alternative Lengthening of Telomeres activity in human cells and cancers - Corrected ProofJeremy D. Henson, Roger R. Reddel10.1016/j.febslet.2010.06.009FEBS Letters (2010)2010-06-11FEBS Letters2010-06-11REVIEWhttp://www.febsletters.org/article/PIIS0014579310004242/abstract?rss=yesAbstract: The ability of our cells to maintain genomic integrity is fundamental for protection from cancer development. Central to this process is the ability of cells to recognize and repair DNA damage and progress through the cell cycle in a regulated and orderly manner. In addition, protection of chromosome ends through the proper assembly of telomeres prevents loss of genetic information and aberrant chromosome fusions. Cells derived from patients with ataxia-telangiectasia (A-T) show defects in cell cycle regulation, abnormal responses to DNA breakage, and chromosomal end-to-end fusions. The identification and characterization of the ATM (ataxia-telangiectasia, mutated) gene product has provided an essential tool for researchers in elucidating cellular mechanisms involved in cell cycle control, DNA repair, and chromosomal stability.Multiple roles of ATM in monitoring and maintaining DNA integrity - Corrected ProofFrederick A. Derheimer, Michael B. Kastan10.1016/j.febslet.2010.05.031FEBS Letters (2010)2010-05-24FEBS Letters2010-05-24REVIEWhttp://www.febsletters.org/article/PIIS0014579310004308/abstract?rss=yesAbstract: Homologous recombination is suppressed at normal length telomere sequences. In contrast, telomere recombination is allowed when telomeres erode in the absence of telomerase activity or as a consequence of nucleolytic degradation or incomplete replication. Here, we review the mechanisms that contribute to regulating mitotic homologous recombination at telomeres and the role of these mechanisms in signalling short telomeres in the budding yeast Saccharomyces cerevisiae.Regulation of homologous recombination at telomeres in budding yeast - Corrected ProofNadine Eckert-Boulet, Michael Lisby10.1016/j.febslet.2010.05.037FEBS Letters (2010)2010-05-24FEBS Letters2010-05-24REVIEWhttp://www.febsletters.org/article/PIIS0014579310004126/abstract?rss=yesAbstract: Dyskeratosis congenita (DC) was originally defined as a rare inherited bone marrow failure (BMF) syndrome associated with distinct mucocutaneous features. Today DC is defined by its pathogenetic mechanism and mutations in components of the telomere maintenance machinery resulting in excessively short telomeres in highly proliferating tissues. With this new definition the disease spectrum has broadened and ranges from intrauterine growth retardation, cerebellar hypoplasia, and death in early childhood to asymptomatic mutation carriers whose descendants are predisposed to malignancy, BMF, or pulmonary disease. The degree of telomere dysfunction is the major determinant of disease onset and manifestations.Dyskeratosis congenita - Corrected ProofMonica Bessler, David B. Wilson, Philip J. Mason10.1016/j.febslet.2010.05.019FEBS Letters (2010)2010-05-20FEBS Letters2010-05-20REVIEWhttp://www.febsletters.org/article/PIIS001457931000414X/abstract?rss=yesAbstract: Phosphorylation of histone variant H2AX at serine 139, named γH2AX, has been widely used as a sensitive marker for DNA double-strand breaks (DSBs). γH2AX is required for the accumulation of many DNA damage response (DDR) proteins at DSBs. Thus it is believed to be the principal signaling protein involved in DDR and to play an important role in DNA repair. However, only mild defects in DNA damage signaling and DNA repair were observed in H2AX-deficient cells and animals. Such findings prompted us and others to explore H2AX-independent mechanisms in DNA damage response. Here, we will review recent advances in our understanding of H2AX-dependent and independent DNA damage signaling and repair pathways in mammalian cells.Focus on histone variant H2AX: To be or not to be - Uncorrected ProofJingsong Yuan, Rachel Adamski, Junjie Chen10.1016/j.febslet.2010.05.021FEBS Letters (2010)2010-05-20FEBS Letters2010-05-20REVIEWhttp://www.febsletters.org/article/PIIS0014579310004163/abstract?rss=yesAbstract: DNA double strand breaks and blocked or collapsed DNA replication forks are potentially genotoxic lesions that can result in deletions, aneuploidy or cell death. Homologous recombination (HR) is an essential process employed during repair of these forms of damage. HR allows for accurate restoration of the damaged DNA through use of a homologous template for repair. Although inroads have been made towards understanding the mechanisms of HR, ambiguity still surrounds aspects of the process. Until recently, relatively little was known concerning metabolism of postsynaptic RAD51 filaments or how synthesis dependent strand annealing intermediates are processed. This review discusses recent findings implicating RTEL1, HELQ and the Caenorhabditis elegans RAD51 paralog RFS-1 in post-strand exchange events during HR.Metabolism of postsynaptic recombination intermediates - Corrected ProofCarrie A. Adelman, Simon J. Boulton10.1016/j.febslet.2010.05.023FEBS Letters (2010)2010-05-20FEBS Letters2010-05-20REVIEWhttp://www.febsletters.org/article/PIIS0014579310004175/abstract?rss=yesAbstract: Proteins that specifically bind the single-stranded overhang at the ends of telomeres have been identified in a wide range of eukaryotes and play pivotal roles in chromosome end protection and telomere length regulation. Here we summarize recent findings regarding the functions of POT1 proteins in vertebrates and discuss the functional evolution of POT1 proteins following gene duplication in protozoa, plants, nematodes and mice.Pot1 and telomere maintenance - Corrected ProofPeter Baumann, Carolyn Price10.1016/j.febslet.2010.05.024FEBS Letters (2010)2010-05-20FEBS Letters2010-05-20REVIEWhttp://www.febsletters.org/article/PIIS0014579310004199/abstract?rss=yesAbstract: Differences between normal adult tissue stem cells and cancer stem/initiating cells remain poorly defined. For example, it is controversial if cancer stem cells can become fully quiescent, require a stem cell niche, are better at repairing DNA damage than the bulk of the cancer cells, and if and how they regulate symmetric versus asymmetric cell divisions. This minireview will not only provide our personal views to address some of these outstanding questions, but also present evidence that an understanding of telomere dynamics and telomerase activity in normal and cancer stem cells may provide additional insights into how tumors are initiated, and how they should be monitored and treated.Telomeres and telomerase in normal and cancer stem cells - Corrected ProofJerry W. Shay, Woodring E. Wright10.1016/j.febslet.2010.05.026FEBS Letters (2010)2010-05-20FEBS Letters2010-05-20REVIEWhttp://www.febsletters.org/article/PIIS0014579310002814/abstract?rss=yesThis article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.WITHDRAWN: Localization and functional activity of APM1 in root-hair cells and BY-2 cells - Corrected ProofOk Ran Lee, Hyung-Taeg Cho, Deok-Chun Yang10.1016/j.febslet.2010.03.049FEBS Letters (2010)2010-04-12FEBS Letters2010-04-12http://www.febsletters.org/article/PIIS0014579309008916/abstract?rss=yesAbstract: This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.WITHDRAWN: USP14 stabilizes calcineurin and regulates NFAT/AP-1 dependent IL-4 transcription as a novel calcineurin-binding protein - Corrected ProofYijuan Zhang, Yi Zheng, Ran Xu, Hongbo Chen, Yongqiang Zhu, Yangqing Zhang, Caiping Guo, Baozong Li, Zhenghui Wu, Yinglong She, Linbai Ye, Laiqiang Huang10.1016/j.febslet.2009.10.087FEBS Letters (2009)2009-11-06FEBS Letters2009-11-06http://www.febsletters.org/article/PIIS0014579309002348/abstract?rss=yesAbstract: Members of the radical S-adenosylmethionine (AdoMet) superfamily reductively cleave AdoMet to generate the highly reactive 5’-deoxyadenosyl radical which initiates biological transformations by abstraction of a hydrogen atom. We demonstrate that three members of the family: biotin synthase (BioB), lipoyl synthase (LipA) and tyrosine lyase (ThiH) are inhibited in vitro by a combination of the products 5’-deoxyadenosine (DOA) and methionine. These results suggest the observed inhibition is a common feature of the radical AdoMet proteins that form DOA and methionine as products. Addition of 5’-methylthioadenosine / S-adenosylhomocysteine nucleosidase (MTAN) to BioB, LipA or ThiH activity assays removed the product inhibition by catalysing the hydrolysis of DOA and gave an increase in activity.Product inhibition in the radical S-adenosylmethionine family - Accepted ManuscriptMartin R. Challand, Tillman Ziegert, Paul Douglas, Robert J. Wood, Marco Kriek, Nicholas M. Shaw, Peter L. Roach10.1016/j.febslet.2009.03.044FEBS Letters (2009)2009-03-26FEBS Letters2009-03-26