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PMID: 12750463 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Saccharomyces cerevisiae chromatin-assembly factors that act during DNA replication function in the maintenance of genome stability.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 100 ·No. 11 ·2003-05-27 ·Pages 6640-5

Myung K, Pennaneach V, Kats ES, Kolodner RD

Abstract

Some spontaneous gross chromosomal rearrangements (GCRs) seem to result from DNA-replication errors. The chromatin-assembly factor I (CAF-I) and replication-coupling assembly factor (RCAF) complexes function in chromatin assembly during DNA replication and repair and could play a role in maintaining genome stability. Inactivation of CAF-I or RCAF increased the rate of accumulating different types of GCRs including translocations and deletion of chromosome arms with associated de novo telomere addition. Inactivation of CAF-I seems to cause damage that activates the DNA-damage checkpoints, whereas inactivation of RCAF seems to cause damage that activates the DNA-damage and replication checkpoints. Both defects result in increased genome instability that is normally suppressed by these checkpoints, RAD52-dependent recombination, and PIF1-dependent inhibition of de novo telomere addition. Treatment of CAF-I- or RCAF-defective cells with methyl methanesulfonate increased the induction of GCRs compared with that seen for a wild-type strain. These results indicate that coupling of chromatin assembly to DNA replication and DNA repair is critical to maintaining genome stability.

MeSH Terms
Chromatin Assembly Factor-1 Chromosomal Proteins, Non-Histone DNA Damage/genetics DNA Repair/genetics DNA Replication/physiology DNA-Binding Proteins/physiology Mutation Saccharomyces cerevisiae/genetics,metabolism Saccharomyces cerevisiae Proteins/physiology
Chemicals
Chromatin Assembly Factor-1 Chromosomal Proteins, Non-Histone DNA-Binding Proteins Saccharomyces cerevisiae Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Myung Kyungjae
Ludwig Institute for Cancer Research, Cancer Center and Department of Medicine, University of California at San Diego School of Medicine, La Jolla 92093, USA.
Pennaneach Vincent
Kats Ellen S
Kolodner Richard D
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.1232239100
Published
2003-05-27
Epub
2003-00-15
Pages
6640-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC164500
Subset
IM
Grants
NIGMS NIH HHS · R01 GM026017 · United States
NIGMS NIH HHS · R37 GM026017 · United States
NIGMS NIH HHS · GM26017 · United States
External Links
PubMed source DOI: 10.1073/pnas.1232239100 PMC Full Text View journal details
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