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PMID: 17936710 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Ctp1 is a cell-cycle-regulated protein that functions with Mre11 complex to control double-strand break repair by homologous recombination.

Molecular cell ·Vol. 28 ·No. 1 ·2007-10-12 ·Pages 134-46

Limbo O, Chahwan C, Yamada Y, de Bruin RA, Wittenberg C, Russell P

Abstract

The Mre11-Rad50-Nbs1 (MRN) complex is a primary sensor of DNA double-strand breaks (DSBs). Upon recruitment to DSBs, it plays a critical role in catalyzing 5' --> 3' single-strand resection that is required for repair by homologous recombination (HR). Unknown mechanisms repress HR in G1 phase of the cell cycle during which nonhomologous end-joining (NHEJ) is the favored mode of DSB repair. Here we describe fission yeast Ctp1, so-named because it shares conserved domains with the mammalian tumor suppressor CtIP. Ctp1 is recruited to DSBs where it is essential for repair by HR. Ctp1 is required for efficient formation of RPA-coated single-strand DNA adjacent to DSBs, indicating that it functions with the MRN complex in 5' --> 3' resection. Transcription of ctp1(+) is periodic during the cell cycle, with the onset of its expression coinciding with the start of DNA replication. These data suggest that regulation of Ctp1 underlies cell-cycle control of HR.

MeSH Terms
Amino Acid Sequence Cell Cycle/physiology Chromosomal Proteins, Non-Histone/genetics,metabolism DNA Breaks, Double-Stranded DNA Repair DNA-Binding Proteins/genetics,metabolism Endodeoxyribonucleases/genetics,metabolism Exodeoxyribonucleases/genetics,metabolism Humans Molecular Sequence Data Recombination, Genetic Saccharomyces cerevisiae Proteins/genetics,metabolism Schizosaccharomyces/cytology,physiology Schizosaccharomyces pombe Proteins/genetics,metabolism Sequence Alignment Telomere/metabolism Transcription Factors/genetics,metabolism Two-Hybrid System Techniques
Chemicals
Chromosomal Proteins, Non-Histone Ctp1 protein, S pombe DNA-Binding Proteins MBP1 protein, S cerevisiae Nbs1 protein, S pombe Rad50 protein, S pombe Saccharomyces cerevisiae Proteins Schizosaccharomyces pombe Proteins Transcription Factors Endodeoxyribonucleases Exodeoxyribonucleases MRE11 protein, S cerevisiae exodeoxyribonuclease I
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Limbo Oliver
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Chahwan Charly
Yamada Yoshiki
de Bruin Robertus A M
Wittenberg Curt
Russell Paul
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Article Info
Journal
Molecular cell
Abbr.
Mol Cell
ISSN
1097-2765
DOI
10.1016/j.molcel.2007.09.009
Published
2007-10-12
Pages
134-46
Language
English
Region
United States
NLM ID
9802571
PMCID
PMC2066204
Subset
IM
Grants
NIGMS NIH HHS · R01 GM059447-09 · United States
NCI NIH HHS · CA117638 · United States
NIGMS NIH HHS · GM59447 · United States
NIGMS NIH HHS · R01 GM059441-08 · United States
NIGMS NIH HHS · R01 GM059441 · United States
NCI NIH HHS · R01 CA117638-03 · United States
NCI NIH HHS · R01 CA117638 · United States
NCI NIH HHS · CA77325 · United States
NIGMS NIH HHS · GM059441 · United States
NCI NIH HHS · R01 CA077325 · United States
NCI NIH HHS · R01 CA077325-10 · United States
NIGMS NIH HHS · R01 GM059447 · United States
Corrections
CommentIn
PMID: 17996697
External Links
PubMed source DOI: 10.1016/j.molcel.2007.09.009 PMC Full Text View journal details
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