SUMOylation of the α-kleisin subunit of cohesin is required for DNA damage-induced cohesion.
Curr Biol
; 22(17): 1564-75, 2012 Sep 11.
Article
en En
| MEDLINE
| ID: mdl-22771042
ABSTRACT
BACKGROUND:
Cohesion between sister chromatids is fundamental to ensure faithful chromosome segregation during mitosis and accurate repair of DNA damage postreplication. At the molecular level, cohesion establishment involves two defined events, a chromatin binding step and a chromatid entrapment event driven by posttranslational modifications on cohesin subunits.RESULTS:
Here, we show that modification by the small ubiquitin-like protein (SUMO) is required for sister chromatid tethering after DNA damage. We find that all subunits of cohesin become SUMOylated upon exposure to DNA damaging agents or presence of a DNA double-strand break. We have mapped all lysine residues on cohesin's α-kleisin subunit Mcd1 (Scc1) where SUMO can conjugate. We demonstrate that Mcd1 SUMOylation-deficient alleles are still recruited to DSB-proximal regions but are defective in tethering sister chromatids and consequently fail to establish damage-induced cohesion both at DSBs and undamaged chromosomes. Moreover, we demonstrate that the bulk of Mcd1 SUMOylation in response to damage is carried out by the SUMO E3 ligase Nse2, a subunit of the related Smc5-Smc6 complex. SUMOylation occurs in cells with compromised Chk1 kinase activity, necessary for known posttranslational modifications on Mcd1, required for damage-induced cohesion.CONCLUSIONS:
These findings demonstrate that SUMOylation of Mcd1 is a novel prerequisite for the establishment of DNA damage-induced cohesion at DSB-proximal regions and cohesion-associating regions (CARs) genome-wide.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Saccharomyces cerevisiae
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Daño del ADN
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Proteínas Cromosómicas no Histona
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Cromátides
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Proteínas de Ciclo Celular
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Segregación Cromosómica
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Proteínas de Saccharomyces cerevisiae
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Sumoilación
Idioma:
En
Revista:
Curr Biol
Asunto de la revista:
BIOLOGIA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Reino Unido