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PMID: 10913172 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Rfc5, in cooperation with rad24, controls DNA damage checkpoints throughout the cell cycle in Saccharomyces cerevisiae.

Molecular and cellular biology ·Vol. 20 ·No. 16 ·2000-08-00 ·Pages 5888-96

Naiki T, Shimomura T, Kondo T, Matsumoto K, Sugimoto K

Abstract

RAD24 and RFC5 are required for DNA damage checkpoint control in the budding yeast Saccharomyces cerevisiae. Rad24 is structurally related to replication factor C (RFC) subunits and associates with RFC subunits Rfc2, Rfc3, Rfc4, and Rfc5. rad24Delta mutants are defective in all the G(1)-, S-, and G(2)/M-phase DNA damage checkpoints, whereas the rfc5-1 mutant is impaired only in the S-phase DNA damage checkpoint. Both the RFC subunits and Rad24 contain a consensus sequence for nucleoside triphosphate (NTP) binding. To determine whether the NTP-binding motif is important for Rad24 function, we mutated the conserved lysine(115) residue in this motif. The rad24-K115E mutation, which changes lysine to glutamate, confers a complete loss-of-function phenotype, while the rad24-K115R mutation, which changes lysine to arginine, shows no apparent phenotype. Although neither rfc5-1 nor rad24-K115R single mutants are defective in the G(1)- and G(2)/M-phase DNA damage checkpoints, rfc5-1 rad24-K115R double mutants become defective in these checkpoints. Coimmunoprecipitation experiments revealed that Rad24(K115R) fails to interact with the RFC proteins in rfc5-1 mutants. Together, these results indicate that RFC5, like RAD24, functions in all the G(1)-, S- and G(2)/M-phase DNA damage checkpoints and suggest that the interaction of Rad24 with the RFC proteins is essential for DNA damage checkpoint control.

MeSH Terms
Cell Cycle/genetics Cell Cycle Proteins/genetics DNA Replication/genetics DNA-Binding Proteins/genetics Gene Expression Regulation, Fungal Homeodomain Proteins Intracellular Signaling Peptides and Proteins Minor Histocompatibility Antigens Mutation Proto-Oncogene Proteins c-bcl-2 Replication Protein C Repressor Proteins Saccharomyces cerevisiae/cytology,genetics Saccharomyces cerevisiae Proteins
Chemicals
BCL2-related protein A1 Cell Cycle Proteins DNA-Binding Proteins Homeodomain Proteins Intracellular Signaling Peptides and Proteins MATA1 protein, S cerevisiae Minor Histocompatibility Antigens Proto-Oncogene Proteins c-bcl-2 RAD24 protein, S cerevisiae Repressor Proteins Saccharomyces cerevisiae Proteins Replication Protein C
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Naiki T
Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-0814, Japan.
Shimomura T
Kondo T
Matsumoto K
Sugimoto K
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.20.16.5888-5896.2000
Published
2000-08-00
Pages
5888-96
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC86066
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.20.16.5888-5896.2000 PMC Full Text View journal details
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