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PMID: 12944482 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The fission yeast Rad32 (Mre11)-Rad50-Nbs1 complex is required for the S-phase DNA damage checkpoint.

Molecular and cellular biology ·Vol. 23 ·No. 18 ·2003-09-00 ·Pages 6564-73

Chahwan C, Nakamura TM, Sivakumar S, Russell P, Rhind N

Abstract

Mre11, Rad50, and Nbs1 form a conserved heterotrimeric complex that is involved in recombination and DNA damage checkpoints. Mutations in this complex disrupt the S-phase DNA damage checkpoint, the checkpoint which slows replication in response to DNA damage, and cause chromosome instability and cancer in humans. However, how these proteins function and specifically where they act in the checkpoint signaling pathway remain crucial questions. We identified fission yeast Nbs1 by using a comparative genomic approach and showed that the genes for human Nbs1 and fission yeast Nbs1 and that for their budding yeast counterpart, Xrs2, are members of an evolutionarily related but rapidly diverging gene family. Fission yeast Nbs1, Rad32 (the homolog of Mre11), and Rad50 are involved in DNA damage repair, telomere regulation, and the S-phase DNA damage checkpoint. However, they are not required for G(2) DNA damage checkpoint. Our results suggest that a complex of Rad32, Rad50, and Nbs1 acts specifically in the S-phase branch of the DNA damage checkpoint and is not involved in general DNA damage recognition or signaling.

MeSH Terms
Amino Acid Sequence Base Sequence Cell Cycle Proteins/genetics Chromosomal Proteins, Non-Histone/genetics,metabolism Cloning, Molecular Conserved Sequence DNA Damage/physiology DNA-Binding Proteins/genetics,metabolism Endodeoxyribonucleases/genetics,metabolism Evolution, Molecular Exodeoxyribonucleases/genetics,metabolism G2 Phase/genetics Gene Expression Regulation, Fungal Macromolecular Substances Methyl Methanesulfonate/pharmacology Molecular Sequence Data Nuclear Proteins/genetics S Phase/genetics Saccharomyces cerevisiae Proteins/genetics,metabolism Schizosaccharomyces/cytology,drug effects,genetics Schizosaccharomyces pombe Proteins/genetics,metabolism Sequence Homology, Amino Acid Telomere/genetics
Chemicals
Cell Cycle Proteins Chromosomal Proteins, Non-Histone DNA-Binding Proteins Macromolecular Substances NBN protein, human Nbs1 protein, S pombe Nuclear Proteins RAD50 protein, S cerevisiae Saccharomyces cerevisiae Proteins Schizosaccharomyces pombe Proteins XRS2 protein, S cerevisiae Methyl Methanesulfonate Endodeoxyribonucleases Exodeoxyribonucleases MRE11 protein, S cerevisiae Mre11 protein, S pombe
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Chahwan Charly
Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Nakamura Toru M
Sivakumar Sasirekha
Russell Paul
Rhind Nicholas
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.23.18.6564-6573.2003
Published
2003-09-00
Pages
6564-73
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC193710
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.23.18.6564-6573.2003 PMC Full Text View journal details
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