Journal
EXPERIMENTAL CELL RESEARCH
Volume 329, Issue 1, Pages 9-17Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2014.08.025
Keywords
DNA repair; DNA damage response; Ubiquitin; Proteasome Protein degradation; Valosin-containing protein VCP; Cdc48
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Funding
- Swedish Research Council [VR-M 2012-2155, VR-NT 2012-3949]
- Swedish Cancer Society [CAN 2012/679]
- European community's Seventh Framework Programme FP7 [264508]
- Karolinska Institute
- Swedish Research Council
- Netherlands Organization for Scientific Research (NWO) [863.11.007]
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The ordered assembly of DNA repair factors on chromatin has been studied in great detail, whereas we are only beginning to realize that selective extraction of proteins from chromatin plays a central role in the DNA damage response. Interestingly, the protein modifier ubiquitin not only regulates the well-documented recruitment of repair proteins, but also governs the temporally and spatially controlled extraction of proteins from DNA lesions. The facilitator of protein extraction is the ubiquitin-dependent ATPase valosin-containing protein (VCP)/p97 complex, which, through its segregase activity, directly extracts ubiquitylated proteins from chromatin. In this review, we summarize recent studies that uncovered this important role of VCP/p97 in the cellular response to genomic insults and discuss how ubiquitin regulates two intuitively counteracting activities at sites of DNA damage. (C) 2014 Elsevier Inc. All rights reserved.
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