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

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 fork...

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Detalles Bibliográficos
Autores: Zapatka, Mariel, Pociño Merino, Irene, Heluani-Gahete, Hayat, Bermúdez López, Marcelino, Tarrés Escalona, Marc, Ibars Estiarte, Eva Irene, Solé-Soler, Roger, Gutiérrez-Escribano, Pilar, Apostolova, Sonia, Casas Herranz, Celia, Aragon, Luis, Wellinger, Ralf Erik, Colomina i Gabarrella, Neus, Torres Rosell, Jordi
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10459.1/68304
Acceso en línea:https://doi.org/10.1016/j.celrep.2019.10.123
http://hdl.handle.net/10459.1/68304
Access Level:acceso abierto
Palabra clave:Smc5
Nse2
Mms21
SUMO
Mph1
DNA damage tolerance
Fork regression
DNA replication
Yeast
Chromosome
Descripción
Sumario: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.

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