title: Should I stay or should I go: VCP/p97-mediated chromatin extraction in the DNA damage response.
abstract: 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.
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, von Eulers väg 3, S-17177 Stockholm, Sweden. Electronic address: nico.dantuma@ki.se.
authors.forename: Nico P
authors.initials: NP
authors.lastname: Dantuma
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, von Eulers väg 3, S-17177 Stockholm, Sweden.
authors.forename: Klara
authors.initials: K
authors.lastname: Acs
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The Netherlands. Electronic address: M.Luijsterburg@lumc.nl.
authors.forename: Martijn S
authors.initials: MS
authors.lastname: Luijsterburg
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism*; D022004:Chromosome Structures; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D025801:Ubiquitin / Q000378:metabolism*; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D025801:Ubiquitin; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein
keywords: Cdc48; DNA damage response; DNA repair; Proteasome; Protein degradation; Ubiquitin; Valosin-containing protein VCP