NuMA promotes homologous recombination repair by regulating the accumulation of the ISWI ATPase SNF2h at DNA breaks

Pierre Alexandre Vidi, Jing Liu, Daniela Salles, Swaathi Jayaraman, George Dorfman, Matthew Gray, Patricia Abad, Prabhas V. Moghe, Joseph M. Irudayaraj, Lisa Wiesmüller, Sophie A. Lelièvre

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Chromatin remodeling factors play an active role in the DNA damage response by shaping chromatin to facilitate the repair process. The spatiotemporal regulation of these factors is key to their function, yet poorly understood. We report that the structural nuclear protein NuMA accumulates at sites of DNA damage in a poly[ADP-ribose]ylation-dependent manner and functionally interacts with the ISWI ATPase SNF2h/SMARCA5, a chromatin remodeler that facilitates DNA repair. NuMA coimmunoprecipitates with SNF2h, regulates its diffusion in the nucleoplasm and controls its accumulation at DNA breaks. Consistent with NuMA enabling SNF2h function, cells with silenced NuMA exhibit reduced chromatin decompaction after DNA cleavage, lesser focal recruitment of homologous recombination repair factors, impaired DNA double-strand break repair in chromosomal (but not in episomal) contexts and increased sensitivity to DNA cross-linking agents. These findings reveal a structural basis for the orchestration of chromatin remodeling whereby a scaffold protein promotes genome maintenance by directing a remodeler to DNA breaks.

Original languageEnglish (US)
Pages (from-to)6365-6379
Number of pages15
JournalNucleic acids research
Volume42
Issue number10
DOIs
StatePublished - Jun 2 2014

All Science Journal Classification (ASJC) codes

  • Genetics

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