USP7 is a SUMO deubiquitinase essential for DNA replication

Emilio Lecona; Sara Rodriguez-Acebes; Julia Specks; Andres J Lopez-Contreras; Isabel Ruppen; Matilde Murga; Javier Muñoz; Juan Mendez; Oscar Fernandez-Capetillo

doi:10.1038/nsmb.3185

USP7 is a SUMO deubiquitinase essential for DNA replication

Emilio Lecona, Sara Rodriguez-Acebes, Julia Specks, Andres J Lopez-Contreras, Isabel Ruppen, Matilde Murga, Javier Muñoz, Juan Mendez, Oscar Fernandez-Capetillo

71 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Nature Structural and Molecular Biology
Volume	23
Issue number	4
Pages (from-to)	270-277
Number of pages	8
ISSN	1545-9993
DOIs	https://doi.org/10.1038/nsmb.3185
Publication status	Published - 5 Apr 2016

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title = "USP7 is a SUMO deubiquitinase essential for DNA replication",

abstract = "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.",

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AU - Lecona, Emilio

AU - Rodriguez-Acebes, Sara

AU - Specks, Julia

AU - Lopez-Contreras, Andres J

AU - Ruppen, Isabel

AU - Murga, Matilde

AU - Muñoz, Javier

AU - Mendez, Juan

AU - Fernandez-Capetillo, Oscar

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AB - 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.

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USP7 is a SUMO deubiquitinase essential for DNA replication

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