The Sm core components of small nuclear ribonucleoproteins promote homologous recombination repair

Abstract

DNA Double strand breaks (DSBs) are highly hazardous to the cell, and are repaired predominantly via non-homologous end joining (NHEJ) and homologous recombination (HR). Using DSB-mimicking DNA templates, our proteomic studies identified a group of Sm core proteins of small nuclear ribonucleoproteins (snRNPs) as potential DSB-associated proteins. We further confirmed that these Sm proteins were recruited to laser-induced DNA damage sites, and co-localized with established DNA damage repair factors. Depletion of Sm-D3 or Sm-B induced accumulation of γ-H2AX, and impaired the repair efficiency of HR, but not NHEJ. Furthermore, disruption of Sm-D3 reduced the protein level of HR factors, especially RAD51 and CHK1, but caused no change in the expression of repair factors involved in NHEJ. Mechanistically, Sm-D3 proteins bound RAD51, suppressed the ubiquitination of RAD51, and mediated the stabilization of RAD51; Sm-D3 depletion particularly impacted the level of RAD51 and CHK1 on damaged chromatin. As such, our studies characterized a role of Sm proteins in HR repair, via a new mechanism that is distinct from their conventional functions in RNA processing and gene regulation, but consistent with their direct recruitment to DNA damage sites and association with repair factors.

Keywords: DNA repair; Homologous recombination; Sm proteins; SnRNP.