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PMID: 12196391 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Telomere binding of checkpoint sensor and DNA repair proteins contributes to maintenance of functional fission yeast telomeres.

Genetics ·Vol. 161 ·No. 4 ·2002-08-00 ·Pages 1437-52

Nakamura TM, Moser BA, Russell P

Abstract

Telomeres, the ends of linear chromosomes, are DNA double-strand ends that do not trigger a cell cycle arrest and yet require checkpoint and DNA repair proteins for maintenance. Genetic and biochemical studies in the fission yeast Schizosaccharomyces pombe were undertaken to understand how checkpoint and DNA repair proteins contribute to telomere maintenance. On the basis of telomere lengths of mutant combinations of various checkpoint-related proteins (Rad1, Rad3, Rad9, Rad17, Rad26, Hus1, Crb2, Chk1, Cds1), Tel1, a telomere-binding protein (Taz1), and DNA repair proteins (Ku70, Rad32), we conclude that Rad3/Rad26 and Tel1/Rad32 represent two pathways required to maintain telomeres and prevent chromosome circularization. Rad1/Rad9/Hus1/Rad17 and Ku70 are two additional epistasis groups, which act in the Rad3/Rad26 pathway. However, Rad3/Rad26 must have additional target(s), as cells lacking Tel1/Rad32, Rad1/Rad9/Hus1/Rad17, and Ku70 groups did not circularize chromosomes. Cells lacking Rad3/Rad26 and Tel1/Rad32 senesced faster than a telomerase trt1Delta mutant, suggesting that these pathways may contribute to telomere protection. Deletion of taz1 did not suppress chromosome circularization in cells lacking Rad3/Rad26 and Tel1/Rad32, also suggesting that two pathways protect telomeres. Chromatin immunoprecipitation analyses found that Rad3, Rad1, Rad9, Hus1, Rad17, Rad32, and Ku70 associate with telomeres. Thus, checkpoint sensor and DNA repair proteins contribute to telomere maintenance and protection through their association with telomeres.

MeSH Terms
Cell Cycle Proteins/genetics,metabolism Checkpoint Kinase 2 DNA Ligases/genetics,metabolism Endonucleases/genetics,metabolism Epistasis, Genetic Exodeoxyribonucleases Fungal Proteins/genetics,metabolism Genes, cdc/physiology Intracellular Signaling Peptides and Proteins Mutation Protein Kinases/genetics,metabolism Protein Serine-Threonine Kinases Saccharomyces cerevisiae/genetics,metabolism Saccharomyces cerevisiae Proteins Schizosaccharomyces/genetics,metabolism Schizosaccharomyces pombe Proteins/genetics,metabolism Telomere/genetics,metabolism
Chemicals
Cell Cycle Proteins Fungal Proteins Intracellular Signaling Peptides and Proteins Saccharomyces cerevisiae Proteins Schizosaccharomyces pombe Proteins Protein Kinases Checkpoint Kinase 2 Protein Serine-Threonine Kinases TEL1 protein, S cerevisiae rad3 protein, S pombe tel1 protein, S pombe Endonucleases Exodeoxyribonucleases Mre11 protein, S pombe DNA Ligases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Nakamura Toru M
Departments of Molecular Biology and Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA. nakamut@scripps.edu
Moser Bettina A
Russell Paul
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Article Info
Journal
Genetics
Abbr.
Genetics
ISSN
0016-6731
DOI
10.1093/genetics/161.4.1437
Email
nakamut@scripps.edu
Published
2002-08-00
Pages
1437-52
Language
English
Region
United States
NLM ID
0374636
PMCID
PMC1462227
Subset
IM
External Links
PubMed source DOI: 10.1093/genetics/161.4.1437 PMC Full Text View journal details
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