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 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Nature Structural and Molecular Biology
Vol/bind	23
Udgave nummer	4
Sider (fra-til)	270-277
Antal sider	8
ISSN	1545-9993
DOI	https://doi.org/10.1038/nsmb.3185
Status	Udgivet - 5 apr. 2016

Adgang til dokumentet

10.1038/nsmb.3185

Citationsformater

@article{cbeefbfe25434eed94a1b200a0d6d150,

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.",

author = "Emilio Lecona and Sara Rodriguez-Acebes and Julia Specks and Lopez-Contreras, {Andres J} and Isabel Ruppen and Matilde Murga and Javier Mu{\~n}oz and Juan Mendez and Oscar Fernandez-Capetillo",

year = "2016",

month = apr,

day = "5",

doi = "10.1038/nsmb.3185",

language = "English",

volume = "23",

pages = "270--277",

journal = "Nature Structural and Molecular Biology",

issn = "1545-9993",

publisher = "nature publishing group",

number = "4",

}

TY - JOUR

T1 - USP7 is a SUMO deubiquitinase essential for DNA replication

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

PY - 2016/4/5

Y1 - 2016/4/5

N2 - 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.

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.

U2 - 10.1038/nsmb.3185

DO - 10.1038/nsmb.3185

M3 - Journal article

C2 - 26950370

SN - 1545-9993

VL - 23

SP - 270

EP - 277

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

IS - 4

ER -

USP7 is a SUMO deubiquitinase essential for DNA replication

Abstract

Adgang til dokumentet

Fingeraftryk

Citationsformater