Sumoylation of Smc5 Promotes Error-free Bypass at Damaged Replication Forks.
Cell Rep
; 29(10): 3160-3172.e4, 2019 12 03.
Article
em En
| MEDLINE
| ID: mdl-31801080
ABSTRACT
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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MEDLINE
Assunto principal:
Proteínas de Ciclo Celular
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Proteínas de Saccharomyces cerevisiae
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Replicação do DNA
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Sumoilação
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article