![]() ĪLT mechanisms were first described in the budding yeast Saccharomyces cerevisiae, where cells using ALT are called “survivors”. ![]() The remaining 10–15% of cancers employ telomerase-independent, recombination-based mechanisms, collectively termed alternative lengthening of telomeres (ALT). Indeed, cancer cells need to activate a telomere maintenance mechanism, and in approximately 85–90% of cancers, this occurs through the upregulation of telomerase. This absence of telomere maintenance may have evolved as a barrier to tumorigenesis (reviewed in ). Most human somatic cells do not express sufficient telomerase to prevent telomere shortening, which may be a contributing factor towards human ageing. Telomerase extends telomeres by iterative reverse transcription of a short sequence to the 3′ ends of telomeres, using the RNA subunit as a template. Telomere shortening can be counteracted by a specialized reverse transcriptase called telomerase, which is composed of a protein catalytic subunit and an RNA subunit. Due to incomplete DNA replication and nucleolytic degradation, telomeres shorten with each round of replication, which can eventually lead to a growth arrest, known as replicative senescence, or to apoptosis. Telomeres, nucleoprotein structures located at the ends of linear chromosomes, prevent natural chromosome ends from being recognized as DNA double-strand breaks (DSBs). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: All relevant data are within the paper and its Supporting Information files.įunding: Work in the Chang lab is supported by a Vidi grant (to MC) from the Netherlands Organisation for Scientific Research ( ). Received: MaAccepted: JPublished: July 18, 2016Ĭopyright: © 2016 Claussin, Chang. PLoS Genet 12(7):Įditor: Lea Harrington, University of Montreal/IRIC, CANADA Impediments to telomere replication can be dealt with by post-replication repair mechanisms, which use a newly synthesized sister chromatid as a template to replicate past the impediment, while telomere truncations, likely caused by the collapse of replication forks, can be extended by break-induced replication.Ĭitation: Claussin C, Chang M (2016) Multiple Rad52-Mediated Homology-Directed Repair Mechanisms Are Required to Prevent Telomere Attrition-Induced Senescence in Saccharomyces cerevisiae. We find that Rad52 acts in multiple ways to overcome DNA replication problems at telomeres. In this study, we explore the role of Rad52 during senescence by taking advantage of rad52 separation-of-function mutants. Yeast lacking both telomerase and Rad52, required for almost all recombination, exhibits accelerated senescence, yet no apparent increase in the rate of telomere shortening. Homologous recombination proteins are important for proper telomere function in yeast and mammals. Telomere attrition has been identified as a hallmark of human ageing. Cells with critically short telomeres can enter an arrested state known as senescence. This shortening can be counteracted by an enzyme called telomerase, but in most human somatic cells, there is insufficient expression of telomerase to prevent telomere shortening. The canonical DNA replication machinery is unable to fully replicate DNA at chromosome ends, causing telomeres to shorten with every round of cell division. Telomeres are essential structures located at the ends of chromosomes.
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