Sumoylation of Smc5 Promotes Error-free Bypass at Damaged Replication Forks.


Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
03 12 2019
Historique:
received: 09 04 2019
revised: 25 09 2019
accepted: 29 10 2019
entrez: 5 12 2019
pubmed: 5 12 2019
medline: 29 9 2020
Statut: ppublish

Résumé

Replication of a damaged DNA template can threaten the integrity of the genome, requiring the use of various mechanisms to tolerate DNA lesions. The Smc5/6 complex, together with the Nse2/Mms21 SUMO ligase, plays essential roles in genome stability through undefined tasks at damaged replication forks. Various subunits within the Smc5/6 complex are substrates of Nse2, but we currently do not know the role of these modifications. Here we show that sumoylation of Smc5 is targeted to its coiled-coil domain, is upregulated by replication fork damage, and participates in bypass of DNA lesions. smc5-KR mutant cells display defects in formation of sister chromatid junctions and higher translesion synthesis. Also, we provide evidence indicating that Smc5 sumoylation modulates Mph1-dependent fork regression, acting synergistically with other pathways to promote chromosome disjunction. We propose that sumoylation of Smc5 enhances physical remodeling of damaged forks, avoiding the use of a more mutagenic tolerance pathway.

Identifiants

pubmed: 31801080
pii: S2211-1247(19)31456-1
doi: 10.1016/j.celrep.2019.10.123
pii:
doi:

Substances chimiques

Cell Cycle Proteins 0
SMC5 protein, S cerevisiae 0
Saccharomyces cerevisiae Proteins 0
DNA 9007-49-2

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3160-3172.e4

Subventions

Organisme : Wellcome Trust
ID : 100955
Pays : United Kingdom

Informations de copyright

Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

Auteurs

Mariel Zapatka (M)

Departament de Ciencies Mediques Basiques, Institut de Recerca Biomedica de Lleida, Universitat de Lleida, 25198 Lleida, Spain.

Irene Pociño-Merino (I)

Departament de Ciencies Mediques Basiques, Institut de Recerca Biomedica de Lleida, Universitat de Lleida, 25198 Lleida, Spain.

Hayat Heluani-Gahete (H)

CABIMER-Universidad de Sevilla, Avenida Americo Vespucio sn, 41092 Sevilla, Spain.

Marcelino Bermúdez-López (M)

Departament de Ciencies Mediques Basiques, Institut de Recerca Biomedica de Lleida, Universitat de Lleida, 25198 Lleida, Spain.

Marc Tarrés (M)

Departament de Ciencies Mediques Basiques, Institut de Recerca Biomedica de Lleida, Universitat de Lleida, 25198 Lleida, Spain.

Eva Ibars (E)

Departament de Ciencies Mediques Basiques, Institut de Recerca Biomedica de Lleida, Universitat de Lleida, 25198 Lleida, Spain.

Roger Solé-Soler (R)

Departament de Ciencies Mediques Basiques, Institut de Recerca Biomedica de Lleida, Universitat de Lleida, 25198 Lleida, Spain.

Pilar Gutiérrez-Escribano (P)

MRC London Institute of Medical Sciences, Du Cane Road, London W12 0NN, UK.

Sonia Apostolova (S)

Departament de Ciencies Mediques Basiques, Institut de Recerca Biomedica de Lleida, Universitat de Lleida, 25198 Lleida, Spain.

Celia Casas (C)

Departament de Ciencies Mediques Basiques, Institut de Recerca Biomedica de Lleida, Universitat de Lleida, 25198 Lleida, Spain.

Luis Aragon (L)

MRC London Institute of Medical Sciences, Du Cane Road, London W12 0NN, UK.

Ralf Wellinger (R)

CABIMER-Universidad de Sevilla, Avenida Americo Vespucio sn, 41092 Sevilla, Spain.

Neus Colomina (N)

Departament de Ciencies Mediques Basiques, Institut de Recerca Biomedica de Lleida, Universitat de Lleida, 25198 Lleida, Spain.

Jordi Torres-Rosell (J)

Departament de Ciencies Mediques Basiques, Institut de Recerca Biomedica de Lleida, Universitat de Lleida, 25198 Lleida, Spain. Electronic address: jordi.torres@cmb.udl.cat.

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Classifications MeSH