2026-04-29T07:35:37Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/176812024-11-29T22:23:51Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Lecona, Emilio
author
Rodriguez-Acebes, Sara
author
Specks, Julia
author
Lopez-Contreras, Andres J
author
Ruppen, Isabel
author
Murga, Matilde
author
Muñoz, Javier
author
Mendez, Juan
author
Fernandez-Capetillo, Oscar
funder
Worldwide Cancer Research
funder
Fundación La Marató TV3
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Danish Council for Independent Research
funder
Danish National Research Foundation
funder
Howard Hughes Medical Institute
funder
Botín Foundation
funder
Danish Cancer Society
2024-02-09T09:46:08Z
2024-02-09T09:46:08Z
2016-04
Nat Struct Mol Biol . 2016;23(4):270-7
http://hdl.handle.net/20.500.12105/17681
26950370
10.1038/nsmb.3185
1545-9985
Nature structural & molecular biology
Post-translational modification of proteins by ubiquitin (Ub) and Ub-like modifiers regulates DNA replication. We have previously shown that chromatin around replisomes is rich in SUMO and poor in Ub, whereas mature chromatin exhibits an opposite pattern. How this SUMO-rich, Ub-poor environment is maintained at sites of DNA replication in mammalian cells remains unexplored. Here we identify USP7 as a replisome-enriched SUMO deubiquitinase that is essential for DNA replication. By acting on SUMO and SUMOylated proteins, USP7 counteracts their ubiquitination. Inhibition or genetic deletion of USP7 leads to the accumulation of Ub on SUMOylated proteins, which are displaced away from replisomes. Our findings provide a model explaining the differential accumulation of SUMO and Ub at replication forks and identify an essential role of USP7 in DNA replication that should be considered in the development of USP7 inhibitors as anticancer agents.
eng
USP7 is a SUMO deubiquitinase essential for DNA replication.
journal article
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