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DNA end resection requires constitutive sumoylation of CtIP by CBX4

Isabel Soria-Bretones, Cristina Cepeda-García, Cintia Checa-Rodriguez, Vincent Heyer, Bernardo Reina-San-Martin, Evi Soutoglou and Pablo Huertas ()
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Isabel Soria-Bretones: Universidad de Sevilla
Cristina Cepeda-García: Universidad de Sevilla-CSIC-Universidad Pablo de Olavide
Cintia Checa-Rodriguez: Universidad de Sevilla
Vincent Heyer: Institut de Génétique et de Biologie Moléculaire et Cellulaire
Bernardo Reina-San-Martin: Institut de Génétique et de Biologie Moléculaire et Cellulaire
Evi Soutoglou: Institut de Génétique et de Biologie Moléculaire et Cellulaire
Pablo Huertas: Universidad de Sevilla

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/s41467-017-00183-6

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