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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Moss, Jennifer Tinline-Purvis, Helen Walker, Carol A. Folkes, Lisa K. Stratford, Michael R. Hayles, Jacqueline Hoe, Kwang-Lae Kim, Dong-Uk Park, Han-Oh Kearsey, Stephen E. Fleck, Oliver Holmberg, Christian Nielsen, Olaf Humphrey, Timothy C. |
| Description | Country affiliation: United kingdom Author Affiliation: Moss J ( Department of Oncology, Cancer Research UK-Medical Research Council Gray Institute for Radiation Oncology and Biology, University of Oxford, United Kingdom.) |
| Abstract | Nucleotide synthesis is a universal response to DNA damage, but how this response facilitates DNA repair and cell survival is unclear. Here we establish a role for DNA damage-induced nucleotide synthesis in homologous recombination (HR) repair in fission yeast. Using a genetic screen, we found the Ddb1-Cul4(Cdt)² ubiquitin ligase complex and ribonucleotide reductase (RNR) to be required for HR repair of a DNA double-strand break (DSB). The Ddb1-Cul4(Cdt)² ubiquitin ligase complex is required for degradation of Spd1, an inhibitor of RNR in fission yeast. Accordingly, deleting spd1(+) suppressed the DNA damage sensitivity and the reduced HR efficiency associated with loss of ddb1(+) or cdt2(+). Furthermore, we demonstrate a role for nucleotide synthesis in postsynaptic gap filling of resected ssDNA ends during HR repair. Finally, we define a role for Rad3 (ATR) in nucleotide synthesis and HR through increasing Cdt2 nuclear levels in response to DNA damage. Our findings support a model in which break-induced Rad3 and Ddb1-Cul4(Cdt)² ubiquitin ligase-dependent Spd1 degradation and RNR activation promotes postsynaptic ssDNA gap filling during HR repair. |
| File Format | HTM / HTML |
| ISSN | 08909369 |
| e-ISSN | 15495477 |
| DOI | 10.1101/gad.1970810 |
| Journal | Genes & Development |
| Issue Number | 23 |
| Volume Number | 24 |
| Language | English |
| Publisher | Cold Spring Harbor Laboratory Press |
| Publisher Date | 2010-12-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Discipline Molecular Discipline Biology__semicolon__developmental Discipline Biology__semicolon__genetics__semicolon__cell Discipline Biology Adaptor Proteins, Signal Transducing Metabolism Cell Cycle Proteins Dna-binding Proteins Protein Kinases Schizosaccharomyces Pombe Proteins Schizosaccharomyces Genetics Checkpoint Kinase 2 Dna Breaks, Double-stranded Dna Repair Gene Deletion Nucleotides Recombination, Genetic Ribonucleotide Reductases Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Developmental Biology |
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