| Title: | "DNA end resection, homologous recombination and DNA damage checkpoint activation require CDK1" |
| Author(s): | Ira G; Pellicioli A; Balijja A; Wang X; Fiorani S; Carotenuto W; Liberi G; Bressan D; Wan L; Hollingsworth NM; Haber JE; Foiani M; |
| Address: | "Rosenstiel Center and Department of Biology, Brandeis University, Waltham, Massachusetts 02454-9110, USA" |
| ISSN/ISBN: | 1476-4687 (Electronic) 0028-0836 (Print) 0028-0836 (Linking) |
| Abstract: | "A single double-strand break (DSB) induced by HO endonuclease triggers both repair by homologous recombination and activation of the Mec1-dependent DNA damage checkpoint in budding yeast. Here we report that DNA damage checkpoint activation by a DSB requires the cyclin-dependent kinase CDK1 (Cdc28) in budding yeast. CDK1 is also required for DSB-induced homologous recombination at any cell cycle stage. Inhibition of homologous recombination by using an analogue-sensitive CDK1 protein results in a compensatory increase in non-homologous end joining. CDK1 is required for efficient 5' to 3' resection of DSB ends and for the recruitment of both the single-stranded DNA-binding complex, RPA, and the Rad51 recombination protein. In contrast, Mre11 protein, part of the MRX complex, accumulates at unresected DSB ends. CDK1 is not required when the DNA damage checkpoint is initiated by lesions that are processed by nucleotide excision repair. Maintenance of the DSB-induced checkpoint requires continuing CDK1 activity that ensures continuing end resection. CDK1 is also important for a later step in homologous recombination, after strand invasion and before the initiation of new DNA synthesis" |
| Keywords: | "CDC2 Protein Kinase/*metabolism Cell Cycle/drug effects Cell Cycle Proteins/metabolism Checkpoint Kinase 2 *DNA Damage/drug effects *DNA Repair/genetics DNA, Fungal/genetics/metabolism Genes, Fungal/genetics Mating Factor Nocodazole/pharmacology Peptides/;" |
| Notes: | "MedlineIra, Grzegorz Pellicioli, Achille Balijja, Alitukiriza Wang, Xuan Fiorani, Simona Carotenuto, Walter Liberi, Giordano Bressan, Debra Wan, Lihong Hollingsworth, Nancy M Haber, James E Foiani, Marco eng AI44009/AI/NIAID NIH HHS/ R01 GM050717/GM/NIGMS NIH HHS/ R01 AI044009/AI/NIAID NIH HHS/ GGP030412/TI_/Telethon/Italy R01 GM080600/GM/NIGMS NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. England 2004/10/22 Nature. 2004 Oct 21; 431(7011):1011-7. doi: 10.1038/nature02964" |
