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PMID: 10224249 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

RAD50 and RAD51 define two pathways that collaborate to maintain telomeres in the absence of telomerase.

Genetics ·Vol. 152 ·No. 1 ·1999-05-00 ·Pages 143-52

Le S, Moore JK, Haber JE, Greider CW

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.

MeSH Terms
Adenosine Triphosphatases Blotting, Southern Cell Division Cell Survival DNA Helicases DNA Repair Enzymes DNA-Binding Proteins/genetics,physiology Endodeoxyribonucleases Epistasis, Genetic Exodeoxyribonucleases Fungal Proteins/genetics,physiology Genotype Mutagenesis RNA, Fungal/physiology Rad51 Recombinase Rad52 DNA Repair and Recombination Protein Recombination, Genetic Saccharomyces cerevisiae/genetics Saccharomyces cerevisiae Proteins Telomerase/physiology Telomere/physiology Time Factors
Chemicals
DNA-Binding Proteins Fungal Proteins RAD50 protein, S cerevisiae RAD52 protein, S cerevisiae RNA, Fungal Rad52 DNA Repair and Recombination Protein Saccharomyces cerevisiae Proteins XRS2 protein, S cerevisiae RAD51 protein, S cerevisiae Rad51 Recombinase Telomerase Endodeoxyribonucleases Exodeoxyribonucleases MRE11 protein, S cerevisiae Adenosine Triphosphatases RAD54 protein, S cerevisiae RAD57 protein, S cerevisiae DNA Helicases DNA Repair Enzymes
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Le S
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Moore J K
Haber J E
Greider C W
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Article Info
Journal
Genetics
Abbr.
Genetics
ISSN
0016-6731
Published
1999-05-00
Pages
143-52
Language
English
Region
United States
NLM ID
0374636
PMCID
PMC1460580
Subset
IM
Grants
NCI NIH HHS · CA 68736 · United States
NCI NIH HHS · CA16519 · United States
NIGMS NIH HHS · GM43080 · United States
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