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PMID: 12897162 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Replication checkpoint kinase Cds1 regulates recombinational repair protein Rad60.

Molecular and cellular biology ·Vol. 23 ·No. 16 ·2003-08-00 ·Pages 5939-46

Boddy MN, Shanahan P, McDonald WH, Lopez-Girona A, Noguchi E, Yates III JR, Russell P

Abstract

Genome integrity is protected by Cds1 (Chk2), a checkpoint kinase that stabilizes arrested replication forks. How Cds1 accomplishes this task is unknown. We report that Cds1 interacts with Rad60, a protein required for recombinational repair in fission yeast. Cds1 activation triggers Rad60 phosphorylation and nuclear delocalization. A Rad60 mutant that inhibits regulation by Cds1 renders cells specifically sensitive to replication fork arrest. Genetic and biochemical studies indicate that Rad60 functions codependently with Smc5 and Smc6, subunits of an SMC (structural maintenance of chromosomes) complex required for recombinational repair. These studies indicate that regulation of Rad60 is an important part of the replication checkpoint response controlled by Cds1. We propose that control of Rad60 regulates recombination events at stalled forks.

MeSH Terms
Amino Acid Sequence Cell Nucleus/metabolism Cell Survival Checkpoint Kinase 2 Chromosomal Proteins, Non-Histone/metabolism Dose-Response Relationship, Drug Dose-Response Relationship, Radiation Immunoblotting Models, Biological Molecular Sequence Data Mutation Phosphorylation Protein Binding Protein Kinases/metabolism Protein Serine-Threonine Kinases Recombination, Genetic Saccharomycetales Schizosaccharomyces pombe Proteins/metabolism
Chemicals
Chromosomal Proteins, Non-Histone Rad60 protein, S pombe Schizosaccharomyces pombe Proteins Protein Kinases Checkpoint Kinase 2 Cds1 protein, S pombe Protein Serine-Threonine Kinases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Boddy Michael N
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Shanahan Paul
McDonald W Hayes
Lopez-Girona Antonia
Noguchi Eishi
Yates III John R
Russell Paul
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.23.16.5939-5946.2003
Published
2003-08-00
Pages
5939-46
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC166335
Subset
IM
Grants
NCRR NIH HHS · P41 RR011823 · United States
NCI NIH HHS · CA81665 · United States
NEI NIH HHS · R01 EY1328801 · United States
NCRR NIH HHS · RR11823 · United States
External Links
PubMed source DOI: 10.1128/MCB.23.16.5939-5946.2003 PMC Full Text View journal details
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