Universität zu Köln

Acs, Klara, Luijsterburg, Martijn S., Ackermann, Leena ORCID: 0000-0001-6405-900X, Salomons, Florian A., Hoppe, Thorsten ORCID: 0000-0002-4734-9352 and Dantuma, Nico P. (2011). The AAA-ATPase VCP/p97 promotes 53BP1 recruitment by removing L3MBTL1 from DNA double-strand breaks. Nat. Struct. Mol. Biol., 18 (12). S. 1345 - 1352. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1545-9985

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Abstract

The accumulation of the human tumor suppressor 53BP1 at DNA damage sites requires the ubiquitin ligases RNF8 and RNF168. As 53BP1 recognizes dimethylated Lys20 in histone H4 (H4K20me2), the requirement for RNF8- and RNF168-mediated ubiquitylation has been unclear. Here we show that RNF8-mediated ubiquitylation facilitates the recruitment of the AAA-ATPase valosin-containing protein (VCP, also known as p97) and its cofactor NPL4 to sites of double-strand breaks. RIDDLE cells, which lack functional RNF168, also show impaired recruitment of VCP to DNA damage. The ATPase activity of VCP promotes the release of the Polycomb protein L3MBTL1 from chromatin, which also binds the H4K20me2 histone mark, thereby facilitating 53BP1 recruitment. Consistent with this, nematodes lacking the VCP orthologs CDC-48.1 or CDC-48.2, or cofactors UFD-1 or NPL-4, are highly sensitive to ionizing radiation. Our data suggest that human RNF8 and RNF168 promote VCP-mediated displacement of L3MBTL1 to unmask 53BP1 chromatin binding sites.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Acs, Klara UNSPECIFIED UNSPECIFIED UNSPECIFIED Luijsterburg, Martijn S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ackermann, Leena UNSPECIFIED orcid.org/0000-0001-6405-900X UNSPECIFIED Salomons, Florian A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoppe, Thorsten UNSPECIFIED orcid.org/0000-0002-4734-9352 UNSPECIFIED Dantuma, Nico P. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-484253
DOI:	10.1038/nsmb.2188
Journal or Publication Title:	Nat. Struct. Mol. Biol.
Volume:	18
Number:	12
Page Range:	S. 1345 - 1352
Date:	2011
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	NEW YORK
ISSN:	1545-9985
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DAMAGE RESPONSE; HISTONE UBIQUITYLATION; STRUCTURAL BASIS; UBIQUITIN; PROTEIN; CHROMATIN; RECOGNITION; METHYLATION; COMPLEX; RNF8 Multiple languages Biochemistry & Molecular Biology; Biophysics; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48425