Universität zu Köln

Franz, Andre, Valledor, Pablo, Ubieto-Capella, Patricia, Pilger, Domenic ORCID: 0000-0001-7339-0685, Galarreta, Antonio ORCID: 0000-0003-2358-7927, Lafarga, Vanesa, Fernandez-Llorente, Alejandro, de la Vega-Barranco, Guillermo, den Brave, Fabian ORCID: 0000-0001-6955-4616, Hoppe, Thorsten, Fernandez-Capetillo, Oscar and Lecona, Emilio (2021). USP7 and VCPFAF1 define the SUMO/Ubiquitin landscape at the DNA replication fork. Cell Reports, 37 (2). CAMBRIDGE: CELL PRESS. ISSN 2211-1247

Full text not available from this repository.

Abstract

The AAA(+) ATPase VCP regulates the extraction of SUMO and ubiquitin-modified DNA replication factors from chromatin. We have previously described that active DNA synthesis is associated with a SUMO-high/ubiquitin-low environment governed by the deubiquitylase USP7. Here, we unveil a functional cooperation between USP7 and VCP in DNA replication, which is conserved from Caenorhabditis elegans to mammals. The role of VCP in chromatin is defined by its cofactor FAF1, which facilitates the extraction of SUMOylated and ubiquitylated proteins that accumulate after the block of DNA replication in the absence of USP7. The inactivation of USP7 and FAF1 is synthetically lethal both in C. elegans and mammalian cells. In addition, USP7 and VCP inhibitors display synergistic toxicity supporting a functional link between deubiquitylation and extraction of chromatin-bound proteins. Our results suggest that USP7 and VCPFAF1 facilitate DNA replication by controlling the balance of SUMO/Ubiquitin-modified DNA replication factors on chromatin.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Franz, Andre UNSPECIFIED UNSPECIFIED UNSPECIFIED Valledor, Pablo UNSPECIFIED UNSPECIFIED UNSPECIFIED Ubieto-Capella, Patricia UNSPECIFIED UNSPECIFIED UNSPECIFIED Pilger, Domenic UNSPECIFIED orcid.org/0000-0001-7339-0685 UNSPECIFIED Galarreta, Antonio UNSPECIFIED orcid.org/0000-0003-2358-7927 UNSPECIFIED Lafarga, Vanesa UNSPECIFIED UNSPECIFIED UNSPECIFIED Fernandez-Llorente, Alejandro UNSPECIFIED UNSPECIFIED UNSPECIFIED de la Vega-Barranco, Guillermo UNSPECIFIED UNSPECIFIED UNSPECIFIED den Brave, Fabian UNSPECIFIED orcid.org/0000-0001-6955-4616 UNSPECIFIED Hoppe, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Fernandez-Capetillo, Oscar UNSPECIFIED UNSPECIFIED UNSPECIFIED Lecona, Emilio UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-597365
DOI:	10.1016/j.celrep.2021.109819
Journal or Publication Title:	Cell Reports
Volume:	37
Number:	2
Date:	2021
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	2211-1247
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language VALOSIN-CONTAINING PROTEIN; FAS-ASSOCIATED FACTOR-1; CELL-DIVISION; UBIQUITIN; SUMO; SEGREGASE; CANCER; DEGRADATION; DESTRUCTION; CDC48/P97 Multiple languages Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59736