2024-03-28T10:04:34Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1655012020-12-13T09:16:23Zcom_10261_134com_10261_1col_10261_387
Soria-Bretones, Isabel
Cepeda-García, Cristina
Checa-Rodríguez, Cintia
Heyer, Vincent
Reina-San-Martin, Bernardo
Soutoglou, Evi
Huertas Sánchez, Pablo
2018-06-01T09:57:02Z
2018-06-01T09:57:02Z
2017
Nature Communications 8(1): 113 (2017)
http://hdl.handle.net/10261/165501
10.1038/s41467-017-00183-6
http://dx.doi.org/10.13039/501100003329
http://dx.doi.org/10.13039/501100000781
http://dx.doi.org/10.13039/100009042
28740167
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 protein that is involved in DNA resection and recombination.
eng
http://creativecommons.org/licenses/by/4.0/
openAccess
DNA end resection requires constitutive sumoylation of CtIP by CBX4
artículo