Publication: A function for cyclin D1 in DNA repair uncovered by protein interactome analyses in human cancers
Issued Date
2011-06-08
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ISSN
14764687
00280836
00280836
Other identifier(s)
2-s2.0-79958254560
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Mahidol University
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SCOPUS
Bibliographic Citation
Nature. Vol.474, No.7350 (2011), 230-234
Suggested Citation
Siwanon Jirawatnotai, Yiduo Hu, Wojciech Michowski, Joshua E. Elias, Lisa Becks, Frederic Bienvenu, Agnieszka Zagozdzon, Tapasree Goswami, Yaoyu E. Wang, Alan B. Clark, Thomas A. Kunkel, Tanja Van Harn, Bing Xia, Mick Correll, John Quackenbush, David M. Livingston, Steven P. Gygi, Piotr Sicinski A function for cyclin D1 in DNA repair uncovered by protein interactome analyses in human cancers. Nature. Vol.474, No.7350 (2011), 230-234. doi:10.1038/nature10155 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/12918
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Title
A function for cyclin D1 in DNA repair uncovered by protein interactome analyses in human cancers
Other Contributor(s)
Harvard Medical School
Mahidol University
Massachusetts College of Pharmacy and Health Sciences
Dana-Farber Cancer Institute
National Institutes of Health, Bethesda
Rutgers Robert Wood Johnson Medical School at New Brunswick
Harvard School of Public Health
Stanford University School of Medicine
Universite de Montpellier
Mahidol University
Massachusetts College of Pharmacy and Health Sciences
Dana-Farber Cancer Institute
National Institutes of Health, Bethesda
Rutgers Robert Wood Johnson Medical School at New Brunswick
Harvard School of Public Health
Stanford University School of Medicine
Universite de Montpellier
Abstract
Cyclin D1 is a component of the core cell cycle machinery 1 . Abnormally high levels of cyclin D1 are detected in many human cancer types 2 . To elucidate the molecular functions of cyclin D1 in human cancers, we performed a proteomic screen for cyclin D1 protein partners in several types of human tumours. Analyses of cyclin D1 interactors revealed a network of DNA repair proteins, including RAD51, a recombinase that drives the homologous recombination process. We found that cyclin D1 directly binds RAD51, and that cyclin D1-RAD51 interaction is induced by radiation. Like RAD51, cyclin D1 is recruited to DNA damage sites in a BRCA2-dependent fashion. Reduction of cyclin D1 levels in human cancer cells impaired recruitment of RAD51 to damaged DNA, impeded the homologous recombination-mediated DNA repair, and increased sensitivity of cells to radiation in vitro and in vivo. This effect was seen in cancer cells lacking the retinoblastoma protein, which do not require D-cyclins for proliferation. These findings reveal an unexpected function of a core cell cycle protein in DNA repair and suggest that targeting cyclin D1 may be beneficial also in retinoblastoma-negative cancers which are currently thought to be unaffected by cyclin D1 inhibition. © 2011 Macmillan Publishers Limited. All rights reserved.