The role of MRN in the S-phase DNA damage checkpoint is independent of its Ctp1-dependent roles in double-strand break repair and checkpoint signaling
UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyDocument Type
Journal ArticlePublication Date
2009-02-13Keywords
Chromosomal Proteins, Non-Histone*DNA Breaks, Double-Stranded
*DNA Repair
DNA-Binding Proteins
Exodeoxyribonucleases
Meiosis
Microbial Viability
Mutation
Phenotype
Recombination, Genetic
*S Phase
Schizosaccharomyces
Schizosaccharomyces pombe Proteins
*Signal Transduction
Spores, Fungal
Telomere
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
The Mre11-Rad50-Nbs1 (MRN) complex has many biological functions: processing of double-strand breaks in meiosis, homologous recombination, telomere maintenance, S-phase checkpoint, and genome stability during replication. In the S-phase DNA damage checkpoint, MRN acts both in activation of checkpoint signaling and downstream of the checkpoint kinases to slow DNA replication. Mechanistically, MRN, along with its cofactor Ctp1, is involved in 5' resection to create single-stranded DNA that is required for both signaling and homologous recombination. However, it is unclear whether resection is essential for all of the cellular functions of MRN. To dissect the various roles of MRN, we performed a structure-function analysis of nuclease dead alleles and potential separation-of-function alleles analogous to those found in the human disease ataxia telangiectasia-like disorder, which is caused by mutations in Mre11. We find that several alleles of rad32 (the fission yeast homologue of mre11), along with ctp1Delta, are defective in double-strand break repair and most other functions of the complex, but they maintain an intact S phase DNA damage checkpoint. Thus, the MRN S-phase checkpoint role is separate from its Ctp1- and resection-dependent role in double-strand break repair. This observation leads us to conclude that other functions of MRN, possibly its role in replication fork metabolism, are required for S-phase DNA damage checkpoint function.Source
Mol Biol Cell. 2009 Apr;20(7):2096-107. Epub 2009 Feb 11. Link to article on publisher's site
DOI
10.1091/mbc.E08-09-0986Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39379PubMed ID
19211838Related Resources
ae974a485f413a2113503eed53cd6c53
10.1091/mbc.E08-09-0986