BRCA1-associated exclusion of 53BP1 from DNA damage sites underlies temporal control of DNA repair.

Journal of Cell Science
J Ross ChapmanStephen P Jackson

Abstract

Following irradiation, numerous DNA-damage-responsive proteins rapidly redistribute into microscopically visible subnuclear aggregates, termed ionising-radiation-induced foci (IRIF). How the enrichment of proteins on damaged chromatin actually relates to DNA repair remains unclear. Here, we use super-resolution microscopy to examine the spatial distribution of BRCA1 and 53BP1 proteins within single IRIF at subdiffraction-limit resolution, yielding an unprecedented increase in detail that was not previously apparent by conventional microscopy. Consistent with a role for 53BP1 in promoting DNA double-strand break repair by non-homologous end joining, 53BP1 enrichment in IRIF is most prominent in the G0/G1 cell cycle phases, where it is enriched in dense globular structures. By contrast, as cells transition through S phase, the recruitment of BRCA1 into the core of IRIF is associated with an exclusion of 53BP1 to the focal periphery, leading to an overall reduction of 53BP1 occupancy at DNA damage sites. Our data suggest that the BRCA1-associated IRIF core corresponds to chromatin regions associated with repair by homologous recombination, and the enrichment of BRCA1 in IRIF represents a temporal switch in the DNA repair program. ...Continue Reading

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Citations

May 21, 2013·DNA Repair·Yannick Auclair, Stéphane Richard
Aug 8, 2013·DNA Repair·Anastas Gospodinov, Zdenko Herceg
Aug 7, 2013·Mutation Research·Ralph Scully, Anyong Xie
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