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Nat Commun. 2017 Jul 24;8(1):113. doi: 10.1038/s41467-017-00183-6.

DNA end resection requires constitutive sumoylation of CtIP by CBX4.

Author information

1
Departamento de Genética, Universidad de Sevilla, Sevilla, 41080, Spain.
2
Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Sevilla, 41092, Spain.
3
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, 67404, France.
4
Institut National de la Santé et de la Recherche Médicale U964, Illkirch, 67404, France.
5
Centre National de Recherche Scientifique UMR7104, Illkirch, 67404, France.
6
Université de Strasbourg, Illkirch, 67081, France.
7
Departamento de Genética, Universidad de Sevilla, Sevilla, 41080, Spain. pablo.huertas@cabimer.es.
8
Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Sevilla, 41092, Spain. pablo.huertas@cabimer.es.

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.The choice between non-homologous end-joining and homologous recombination to repair a DNA double-strand break depends on activation of the end resection machinery. Here the authors show that SUMO E3 ligase CBX4 sumoylates subpopulation of CtIP to regulate recruitment to breaks and resection.

PMID:
28740167
PMCID:
PMC5524638
DOI:
10.1038/s41467-017-00183-6
[Indexed for MEDLINE]
Free PMC Article

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