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DNA end resection requires constitutive sumoylation of CtIP by CBX4

Opened Access DNA end resection requires constitutive sumoylation of CtIP by CBX4

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Autor: Soria Bretones, Isabel
Cepeda García, Cristina
Checa Rodriguez, Cintia
Heyer, Vincent
Reina San Martín, Bernardo
Soutoglou, Evi
Huertas Sánchez, Pablo
Fecha: 2017
Publicado en: Nature Communications, 8 (113)
Tipo de documento: Artículo
Resumen: DNA breaks are complex DNA lesions that can be repaired by two alternative mechanisms: non-homologous end-joining and homologous recombination. The decision between them depends on the activation of the DNA resection machinery, which blocks non-homologous end-joining and stimulates recombination. On the other hand, post-translational modifications play a critical role in DNA repair. We have found that the SUMO E3 ligase CBX4 controls resection through the key factor CtIP. Indeed, CBX4 depletion impairs CtIP constitutive sumoylation and DNA end processing. Importantly, mutating lysine 896 in CtIP recapitulates the CBX4-depletion phenotype, blocks homologous recombination and increases genomic instability. Artificial fusion of CtIP and SUMO suppresses the effects of both the non-sumoylatable CtIP mutant and CBX4 depletion. Mechanistically, CtIP sumoylation is essential for its recruitment to damaged DNA. In summary, sumoylation of CtIP at lysine 896 defines a subpopulation of the protei...
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Cita: Soria Bretones, I., Cepeda García, C., Checa Rodriguez, C., Heyer, V., Reina San Martín, B., Soutoglou, E. y Huertas Sánchez, P. (2017). DNA end resection requires constitutive sumoylation of CtIP by CBX4. Nature Communications, 8 (113)
Tamaño: 1.930Mb
Formato: PDF

URI: http://hdl.handle.net/11441/63913

DOI: 10.1038/s41467-017-00183-6

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