The Mph1 helicase can promote telomere uncapping and premature senescence in budding yeast.

Double strand breaks (DSBs) can be repaired via either Non-Homologous End Joining (NHEJ) or Homology directed Repair (HR). Telomeres, which resemble DSBs, are refractory to repair events in order to prevent chromosome end fusions and genomic instability. In some rare instances telomeres engage in Br...

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Autores principales: Sarah Luke-Glaser, Brian Luke
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Publicado: Public Library of Science (PLoS) 2012
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Acceso en línea:https://doaj.org/article/cdc449df9d264fcda551aedd1e51e150
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spelling oai:doaj.org-article:cdc449df9d264fcda551aedd1e51e1502021-11-18T07:10:37ZThe Mph1 helicase can promote telomere uncapping and premature senescence in budding yeast.1932-620310.1371/journal.pone.0042028https://doaj.org/article/cdc449df9d264fcda551aedd1e51e1502012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22848695/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Double strand breaks (DSBs) can be repaired via either Non-Homologous End Joining (NHEJ) or Homology directed Repair (HR). Telomeres, which resemble DSBs, are refractory to repair events in order to prevent chromosome end fusions and genomic instability. In some rare instances telomeres engage in Break-Induced Replication (BIR), a type of HR, in order to maintain telomere length in the absence of the enzyme telomerase. Here we have investigated how the yeast helicase, Mph1, affects DNA repair at both DSBs and telomeres. We have found that overexpressed Mph1 strongly inhibits BIR at internal DSBs however allows it to proceed at telomeres. Furthermore, while overexpressed Mph1 potently inhibits NHEJ at telomeres it has no effect on NHEJ at DSBs within the chromosome. At telomeres Mph1 is able to promote telomere uncapping and the accumulation of ssDNA, which results in premature senescence in the absence of telomerase. We propose that Mph1 is able to direct repair towards HR (thereby inhibiting NHEJ) at telomeres by remodeling them into a nuclease-sensitive structure, which promotes the accumulation of a recombinogenic ssDNA intermediate. We thus put forward that Mph1 is a double-edge sword at the telomere, it prevents NHEJ, but promotes senescence in cells with dysfunctional telomeres by increasing the levels of ssDNA.Sarah Luke-GlaserBrian LukePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 7, p e42028 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Sarah Luke-Glaser
Brian Luke
The Mph1 helicase can promote telomere uncapping and premature senescence in budding yeast.
description Double strand breaks (DSBs) can be repaired via either Non-Homologous End Joining (NHEJ) or Homology directed Repair (HR). Telomeres, which resemble DSBs, are refractory to repair events in order to prevent chromosome end fusions and genomic instability. In some rare instances telomeres engage in Break-Induced Replication (BIR), a type of HR, in order to maintain telomere length in the absence of the enzyme telomerase. Here we have investigated how the yeast helicase, Mph1, affects DNA repair at both DSBs and telomeres. We have found that overexpressed Mph1 strongly inhibits BIR at internal DSBs however allows it to proceed at telomeres. Furthermore, while overexpressed Mph1 potently inhibits NHEJ at telomeres it has no effect on NHEJ at DSBs within the chromosome. At telomeres Mph1 is able to promote telomere uncapping and the accumulation of ssDNA, which results in premature senescence in the absence of telomerase. We propose that Mph1 is able to direct repair towards HR (thereby inhibiting NHEJ) at telomeres by remodeling them into a nuclease-sensitive structure, which promotes the accumulation of a recombinogenic ssDNA intermediate. We thus put forward that Mph1 is a double-edge sword at the telomere, it prevents NHEJ, but promotes senescence in cells with dysfunctional telomeres by increasing the levels of ssDNA.
format article
author Sarah Luke-Glaser
Brian Luke
author_facet Sarah Luke-Glaser
Brian Luke
author_sort Sarah Luke-Glaser
title The Mph1 helicase can promote telomere uncapping and premature senescence in budding yeast.
title_short The Mph1 helicase can promote telomere uncapping and premature senescence in budding yeast.
title_full The Mph1 helicase can promote telomere uncapping and premature senescence in budding yeast.
title_fullStr The Mph1 helicase can promote telomere uncapping and premature senescence in budding yeast.
title_full_unstemmed The Mph1 helicase can promote telomere uncapping and premature senescence in budding yeast.
title_sort mph1 helicase can promote telomere uncapping and premature senescence in budding yeast.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/cdc449df9d264fcda551aedd1e51e150
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