title: RAD50 and RAD51 define two pathways that collaborate to maintain telomeres in the absence of telomerase.
abstract: Telomere length is maintained by the de novo addition of telomere repeats by telomerase, yet recombination can elongate telomeres in the absence of telomerase. When the yeast telomerase RNA component, TLC1, is deleted, telomeres shorten and most cells die. However, gene conversion mediated by the RAD52 pathway allows telomere lengthening in rare survivor cells. To further investigate the role of recombination in telomere maintenance, we assayed telomere length and the ability to generate survivors in several isogenic DNA recombination mutants, including rad50, rad51, rad52, rad54, rad57, xrs2, and mre11. The rad51, rad52, rad54, and rad57 mutations increased the rate of cell death in the absence of TLC1. In contrast, although the rad50, xrs2, and mre11 strains initially had short telomeres, double mutants with tlc1 did not affect the rate of cell death, and survivors were generated at later times than tlc1 alone. While none of the double mutants of recombination genes and tlc1 (except rad52 tlc1) blocked the ability to generate survivors, a rad50 rad51 tlc1 triple mutant did not allow the generation of survivors. Thus RAD50 and RAD51 define two separate pathways that collaborate to allow cells to survive in the absence of telomerase.
authors.affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: S
authors.initials: S
authors.lastname: Le
authors.forename: J K
authors.initials: JK
authors.lastname: Moore
authors.forename: J E
authors.initials: JE
authors.lastname: Haber
authors.forename: C W
authors.initials: CW
authors.lastname: Greider
mesh_terms: D000251:Adenosine Triphosphatases; D015139:Blotting, Southern; D002455:Cell Division; D002470:Cell Survival; D004265:DNA Helicases; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004706:Endodeoxyribonucleases; D004843:Epistasis, Genetic; D005090:Exodeoxyribonucleases; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D005838:Genotype; D016296:Mutagenesis; D012331:RNA, Fungal / Q000502:physiology*; D051135:Rad51 Recombinase; D051721:Rad52 DNA Repair and Recombination Protein; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D019098:Telomerase / Q000502:physiology*; D016615:Telomere / Q000502:physiology*; D013997:Time Factors
chemical_list: D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C086930:RAD50 protein, S cerevisiae; C497197:RAD52 protein, S cerevisiae; D012331:RNA, Fungal; D051721:Rad52 DNA Repair and Recombination Protein; D029701:Saccharomyces cerevisiae Proteins; C086929:XRS2 protein, S cerevisiae; C495151:RAD51 protein, S cerevisiae; D051135:Rad51 Recombinase; D019098:Telomerase; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; C094191:MRE11 protein, S cerevisiae; D000251:Adenosine Triphosphatases; C075468:RAD54 protein, S cerevisiae; C071451:RAD57 protein, S cerevisiae; D004265:DNA Helicases; D045643:DNA Repair Enzymes