PMC:6145447 / 83-1083 JSONTXT

{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/6145447","sourcedb":"PMC","sourceid":"6145447","source_url":"https://www.ncbi.nlm.nih.gov/pmc/6145447","text":"DNA double-strand breaks (DSBs) repaired by non-homologous end joining (NHEJ) display limited DNA end processing and chromosomal mobility. In contrast, DSBs undergoing homology-directed repair (HDR) exhibit extensive processing and enhanced motion. The molecular basis for this movement is unknown. Using Xenopus laevis cell-free extracts and mammalian cells, we establish that nuclear actin, WASP and the Arp2/3 complex are recruited to damaged chromatin undergoing HDR. We demonstrate that nuclear actin polymerization is required for the migration of a subset of DSBs into discrete sub-nuclear clusters. Actin-driven movements specifically affect DSBs repaired by HDR in G2; inhibition of actin nucleation impairs DNA end-processing and HDR efficiency. In contrast, Arp2/3 is not enriched at DSBs repaired by NHEJ and does not regulate NHEJ. Our findings establish that nuclear actin-based mobility shapes chromatin organization by generating repair domains essential for HDR in eukaryotic 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