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MRX protects telomeric DNA at uncapped telomeres of budding yeast cdc13-1 mutants
Authors:Foster Steven S  Zubko Mikhajlo K  Guillard Sandrine  Lydall David
Affiliation:Institute for Ageing and Health, University of Newcastle, Henry Wellcome Laboratory for Biogerontology Research, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE, UK.
Abstract:MRX, an evolutionally conserved DNA damage response complex composed of Mre11, Rad50 and Xrs2, is involved in DNA double strand break (DSB) repair, checkpoint activation and telomere maintenance. At DSBs, MRX plays a role in generating single stranded DNA (ssDNA) and signalling cell cycle arrest. Here we investigated whether MRX also contributes to generating ssDNA or signalling cell cycle arrest at uncapped telomeres. To investigate the role of MRX, we generated a conditionally degradable Rad50 protein and combined this with cdc13-1, a temperature sensitive mutation in the Cdc13 telomere capping protein. We show that Rad50 does not contribute to ssDNA generation or cell cycle arrest in response to cdcl3-1 uncapped telomeres. Instead, we find that Rad50 inhibits ssDNA accumulation and promotes cdc13-1 cell viability, consistent with a major role for MRX in telomere capping.
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