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ID 113748
著者
D'Angiolella, Vincenzo New York University
Donato, Valerio New York University
Forrester, Frances M. New York University
Jeong, Yeon-Tae New York University
Pellacani, Claudia New York University
Saraf, Anita The Stowers Institute for Medical Research
Florens, Laurence The Stowers Institute for Medical Research
Washburn, Michael P. The Stowers Institute for Medical Research|The University of Kansas
Pagano, Michele New York University|Howard Hughes Medical Institute
資料タイプ
学術雑誌論文
抄録
F-box proteins are the substrate binding subunits of SCF (Skp1-Cul1-F-box protein) ubiquitin ligase complexes. Using affinity purifications and mass spectrometry, we identified RRM2 (the ribonucleotide reductase family member 2) as an interactor of the F-box protein cyclin F. Ribonucleotide reductase (RNR) catalyzes the conversion of ribonucleotides to deoxyribonucleotides (dNTPs), which are necessary for both replicative and repair DNA synthesis. We found that, during G2, following CDK-mediated phosphorylation of Thr33, RRM2 is degraded via SCFcyclin F to maintain balanced dNTP pools and genome stability. After DNA damage, cyclin F is downregulated in an ATR-dependent manner to allow accumulation of RRM2. Defective elimination of cyclin F delays DNA repair and sensitizes cells to DNA damage, a phenotype that is reverted by expressing a nondegradable RRM2 mutant. In summary, we have identified a biochemical pathway that controls the abundance of dNTPs and ensures efficient DNA repair in response to genotoxic stress.
掲載誌名
Cell
ISSN
00928674
cat書誌ID
AA00600003
AA12024453
出版者
Elsevier
149
5
開始ページ
1023
終了ページ
1034
発行日
2012-05-25
権利情報
Open Archive
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
歯学系