BRCA2 controls DNA:RNA hybrid level at DSBs by mediating RNase H2 recruitment Academic Article uri icon

abstract

  • DNA double-strand breaks (DSBs) are toxic DNA lesions, which, if not properly repaired, may lead to genomic instability, cell death and senescence. Damage-induced long non-coding RNAs (dilncRNAs) are transcribed from broken DNA ends and contribute to DNA damage response (DDR) signaling. Here we show that dilncRNAs play a role in DSB repair by homologous recombination (HR) by contributing to the recruitment of the HR proteins BRCA1, BRCA2, and RAD51, without affecting DNA-end resection. In S/G2-phase cells, dilncRNAs pair to the resected DNA ends and form DNA:RNA hybrids, which are recognized by BRCA1. We also show that BRCA2 directly interacts with RNase H2, mediates its localization to DSBs in the S/G2 cell-cycle phase, and controls DNA:RNA hybrid levels at DSBs. These results demonstrate that regulated DNA:RNA hybrid levels at DSBs contribute to HR-mediated repair.

authors

  • D'Alessandro, Giuseppina
  • Whelan, Donna Rose
  • Howard, Sean Michael
  • Vitelli, Valerio
  • Renaudin, Xavier
  • Adamowicz, Marek
  • Iannelli, Fabio
  • Jones-Weinert, Corey Winston
  • Lee, MiYoung
  • Matti, Valentina
  • Lee, Wei Ting C
  • Morten, Michael John
  • Venkitaraman, Ashok Raraakrishnan
  • Cejka, Petr
  • Rothenberg, Eli
  • di Fagagna, Fabrizio d'Adda

publication date

  • 2018