@article{1176,
  author = {Britt Adamson and Agata Smogorzewska and Frederic Sigoillot and Randall King and Stephen Elledge},
  title = {A genome-wide homologous recombination screen identifies the RNA-binding protein RBMX as a component of the DNA-damage response.},
  abstract = {<p>Repair of DNA double-strand breaks is critical to genomic stability and the prevention of developmental disorders and cancer. A central pathway for this repair is homologous recombination (HR). Most knowledge of HR is derived from work in prokaryotic and eukaryotic model organisms. We carried out a genome-wide siRNA-based screen in human cells. Among positive regulators of HR we identified networks of DNA-damage-response and pre-mRNA-processing proteins, and among negative regulators we identified a phosphatase network. Three candidate proteins localized to DNA lesions, including RBMX, a heterogeneous nuclear ribonucleoprotein that has a role in alternative splicing. RBMX accumulated at DNA lesions through multiple domains in a poly(ADP-ribose) polymerase 1-dependent manner and promoted HR by facilitating proper BRCA2 expression. Our screen also revealed that off-target depletion of RAD51 is a common source of RNAi false positives, raising a cautionary note for siRNA screens and RNAi-based studies of HR.</p>
},
  year = {2012},
  journal = {Nature cell biology},
  volume = {14},
  pages = {318-28},
  month = {02/2012},
  issn = {1476-4679},
  doi = {10.1038/ncb2426},
  language = {eng},
}