title: MRX protects telomeric DNA at uncapped telomeres of budding yeast cdc13-1 mutants.
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.
authors.affiliation: Institute for Ageing and Health, University of Newcastle, Henry Wellcome Laboratory for Biogerontology Research, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE, UK.
authors.forename: Steven S
authors.initials: SS
authors.lastname: Foster
authors.forename: Mikhajlo K
authors.initials: MK
authors.lastname: Zubko
authors.forename: Sandrine
authors.initials: S
authors.lastname: Guillard
authors.forename: David
authors.initials: D
authors.lastname: Lydall
mesh_terms: D001483:Base Sequence; D002453:Cell Cycle; D004260:DNA Repair; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004706:Endodeoxyribonucleases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005090:Exodeoxyribonucleases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005800:Genes, Fungal; D008954:Models, Biological; D046912:Multiprotein Complexes; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D016615:Telomere / Q000235:genetics / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: C452219:Cdc13 protein, S cerevisiae; D004271:DNA, Fungal; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; C086930:RAD50 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D034501:Telomere-Binding Proteins; C086929:XRS2 protein, S cerevisiae; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; C094191:MRE11 protein, S cerevisiae