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PMID: 10097122 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

DRC1, DNA replication and checkpoint protein 1, functions with DPB11 to control DNA replication and the S-phase checkpoint in Saccharomyces cerevisiae.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 96 ·No. 7 ·1999-03-30 ·Pages 3824-9

Wang H, Elledge SJ

Abstract

In addition to DNA polymerase complexes, DNA replication requires the coordinate action of a series of proteins, including regulators Cdc28/Clb and Dbf4/Cdc7 kinases, Orcs, Mcms, Cdc6, Cdc45, and Dpb11. Of these, Dpb11, an essential BRCT repeat protein, has remained particularly enigmatic. The Schizosaccharomyces pombe homolog of DPB11, cut5, has been implicated in the DNA replication checkpoint as has the POL2 gene with which DPB11 genetically interacts. Here we describe a gene, DRC1, isolated as a dosage suppressor of dpb11-1. DRC1 is an essential cell cycle-regulated gene required for DNA replication. We show that both Dpb11 and Drc1 are required for the S-phase checkpoint, including the proper activation of the Rad53 kinase in response to DNA damage and replication blocks. Dpb11 is the second BRCT-repeat protein shown to control Rad53 function, possibly indicating a general function for this class of proteins. DRC1 and DPB11 show synthetic lethality and reciprocal dosage suppression. The Drc1 and Dpb11 proteins physically associate and function together to coordinate DNA replication and the cell cycle.

MeSH Terms
Amino Acid Sequence Cell Cycle/genetics Cell Cycle Proteins/chemistry,genetics,metabolism DNA Polymerase II/genetics,metabolism DNA Replication Fungal Proteins/genetics,metabolism Genotype Molecular Sequence Data S Phase Saccharomyces cerevisiae/cytology,genetics,growth & development Saccharomyces cerevisiae Proteins Sequence Alignment Sequence Homology, Amino Acid Temperature
Chemicals
Cell Cycle Proteins DPB11 protein, S cerevisiae Fungal Proteins SLD2 protein, S cerevisiae Saccharomyces cerevisiae Proteins DNA Polymerase II
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Wang H
Howard Hughes Medical Institute, Verna and Marrs McLean Department of Biochemistry, Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Elledge S J
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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.96.7.3824
Published
1999-03-30
Pages
3824-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC22379
Subset
IM
Grants
NIGMS NIH HHS · R01 GM044664 · United States
NIGMS NIH HHS · R37 GM044664 · United States
NIGMS NIH HHS · GM4464 · United States
External Links
PubMed source DOI: 10.1073/pnas.96.7.3824 PMC Full Text View journal details
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