FEBS Letters RSS feed: Current Issue. 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/?rss=yesElsevier Inc.en © 2010 Published by Elsevier Inc. All rights reserved. FEBS Letters0014-57935841710 September 2010 © 2010 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.febsletters.org/article/PIIS0014579310006526/abstract?rss=yesEditorial Board10.1016/S0014-5793(10)00652-6FEBS Letters 584, 17 (2010)2010-09-10FEBS Letters2010-09-1058417S0014-5793(10)X0016-3iihttp://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 benefitsTitia de Lange10.1016/j.febslet.2010.07.030FEBS Letters 584, 17 (2010)2010-07-22FEBS Letters2010-07-2258417S0014-5793(10)X0016-3Introduction36733674http://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 integrityFrederick A. Derheimer, Michael B. Kastan10.1016/j.febslet.2010.05.031FEBS Letters 584, 17 (2010)2010-05-24FEBS Letters2010-05-2458417S0014-5793(10)X0016-3DNA Repair36753681http://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 maintenanceBrandon J. Lamarche, Nicole I. Orazio, Matthew D. Weitzman10.1016/j.febslet.2010.07.029FEBS Letters 584, 17 (2010)2010-07-22FEBS Letters2010-07-2258417S0014-5793(10)X0016-3DNA Repair36823695http://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 yeastNadine Eckert-Boulet, Michael Lisby10.1016/j.febslet.2010.05.037FEBS Letters 584, 17 (2010)2010-05-24FEBS Letters2010-05-2458417S0014-5793(10)X0016-3DNA Repair36963702http://www.febsletters.org/article/PIIS0014579310006198/abstract?rss=yesAbstract: DNA double-strand breaks resulting from normal cellular processes including replication and exogenous sources such as ionizing radiation pose a serious risk to genome stability, and cells have evolved different mechanisms for their efficient repair. The two major pathways involved in the repair of double-strand breaks in eukaryotic cells are non-homologous end joining and homologous recombination. Numerous factors affect the decision to repair a double-strand break via these pathways, and accumulating evidence suggests these major repair pathways both cooperate and compete with each other at double-strand break sites to facilitate efficient repair and promote genomic integrity.Collaboration and competition between DNA double-strand break repair pathwaysElizabeth M. Kass, Maria Jasin10.1016/j.febslet.2010.07.057FEBS Letters 584, 17 (2010)2010-08-04FEBS Letters2010-08-0458417S0014-5793(10)X0016-3DNA Repair37033708http://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 intermediatesCarrie A. Adelman, Simon J. Boulton10.1016/j.febslet.2010.05.023FEBS Letters 584, 17 (2010)2010-05-20FEBS Letters2010-05-2058417S0014-5793(10)X0016-3DNA Repair37093716http://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 beJingsong Yuan, Rachel Adamski, Junjie Chen10.1016/j.febslet.2010.05.021FEBS Letters 584, 17 (2010)2010-05-20FEBS Letters2010-05-2058417S0014-5793(10)X0016-3DNA Repair37173724http://www.febsletters.org/article/PIIS0014579310006071/abstract?rss=yesAbstract: Recent years have placed fission yeast at the forefront of telomere research, as this organism combines a high level of conservation with human telomeres and precise genetic manipulability. Here we highlight some of the latest knowledge of fission yeast telomere maintenance and dysfunction, and illustrate how principles arising from fission yeast research are raising novel questions about telomere plasticity and function in all eukaryotes.Fission yeast telomeres forecast the end of the crisisPierre-Marie Dehé, Julia Promisel Cooper10.1016/j.febslet.2010.07.045FEBS Letters 584, 17 (2010)2010-08-02FEBS Letters2010-08-0258417S0014-5793(10)X0016-3Telomere/Telomerase37253733http://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 yeastRaymund J. Wellinger10.1016/j.febslet.2010.06.031FEBS Letters 584, 17 (2010)2010-06-25FEBS Letters2010-06-2558417S0014-5793(10)X0016-3Telomere/Telomerase37343740http://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 MetazoaNuno M.V. Gomes, Jerry W. Shay, Woodring E. Wright10.1016/j.febslet.2010.07.031FEBS Letters 584, 17 (2010)2010-07-23FEBS Letters2010-07-2358417S0014-5793(10)X0016-3Telomere/Telomerase37413751http://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 standJ. Matthew Watson, Karel Riha10.1016/j.febslet.2010.06.017FEBS Letters 584, 17 (2010)2010-06-18FEBS Letters2010-06-1858417S0014-5793(10)X0016-3Telomere/Telomerase37523759http://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 unwindingKatrin Paeschke, Karin R. McDonald, Virginia A. Zakian10.1016/j.febslet.2010.07.007FEBS Letters 584, 17 (2010)2010-07-14FEBS Letters2010-07-1458417S0014-5793(10)X0016-3Telomere/Telomerase37603772http://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 endsSuzanne S. Chan, Sandy Chang10.1016/j.febslet.2010.06.016FEBS Letters 584, 17 (2010)2010-06-18FEBS Letters2010-06-1858417S0014-5793(10)X0016-3Telomere/Telomerase37733778http://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 maintenancePeter Baumann, Carolyn Price10.1016/j.febslet.2010.05.024FEBS Letters 584, 17 (2010)2010-05-20FEBS Letters2010-05-2058417S0014-5793(10)X0016-3Telomere/Telomerase37793784http://www.febsletters.org/article/PIIS001457931000640X/abstract?rss=yesAbstract: A major issue in telomere research is to understand how the integrity of chromosome ends is controlled. Although several nucleoprotein complexes have been described at the telomeres of different organisms, it is still unclear how they confer a structural identity to chromosome ends in order to mask them from DNA repair and to ensure their proper replication. In this review, we describe how telomeric nucleoprotein complexes are structured, comparing different organisms and trying to link these structures to telomere biology. It emerges that telomeres are formed by a complex and specific network of interactions between DNA, RNA and proteins. The fact that these interactions and associated activities are reinforcing each other might help to guaranty the robustness of telomeric functions across the cell cycle and in the event of cellular perturbations. We propose that telomeric nucleoprotein complexes orient cell fate through dynamic transitions in their structures and their organization.Structural identity of telomeric complexesMarie-Josèphe Giraud-Panis, Sabrina Pisano, Anaïs Poulet, Marie-Hélène Le Du, Eric Gilson10.1016/j.febslet.2010.08.004FEBS Letters 584, 17 (2010)2010-08-09FEBS Letters2010-08-0958417S0014-5793(10)X0016-3Telomere/Telomerase37853799http://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 cancersJeremy D. Henson, Roger R. Reddel10.1016/j.febslet.2010.06.009FEBS Letters 584, 17 (2010)2010-06-11FEBS Letters2010-06-1158417S0014-5793(10)X0016-3Telomere/Telomerase38003811http://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 functionSascha Feuerhahn, Nahid Iglesias, Andrea Panza, Antonio Porro, Joachim Lingner10.1016/j.febslet.2010.07.032FEBS Letters 584, 17 (2010)2010-07-23FEBS Letters2010-07-2358417S0014-5793(10)X0016-3Telomere/Telomerase38123818http://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 cellsJerry W. Shay, Woodring E. Wright10.1016/j.febslet.2010.05.026FEBS Letters 584, 17 (2010)2010-05-20FEBS Letters2010-05-2058417S0014-5793(10)X0016-3Telomere/Telomerase38193825http://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 agingIgnacio Flores, Maria A. Blasco10.1016/j.febslet.2010.07.042FEBS Letters 584, 17 (2010)2010-07-30FEBS Letters2010-07-3058417S0014-5793(10)X0016-3Telomere/Telomerase38263830http://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 congenitaMonica Bessler, David B. Wilson, Philip J. Mason10.1016/j.febslet.2010.05.019FEBS Letters 584, 17 (2010)2010-05-20FEBS Letters2010-05-2058417S0014-5793(10)X0016-3Telomere/Telomerase38313838