The RNF138 E3 ligase displaces Ku to promote DNA end resection and regulate DNA repair pathway choice.

Citation:
Ismail, I. H., J. - P. Gagné, M. - M. Genois, H. Strickfaden, D. McDonald, Z. Xu, G. G. Poirier, J. - Y. Masson, and M. J. Hendzel, "The RNF138 E3 ligase displaces Ku to promote DNA end resection and regulate DNA repair pathway choice.", Nature cell biology, vol. 17, issue 11, pp. 1446-57, 2015 Nov.

Abstract:

DNA double-strand breaks (DSBs) are repaired mainly by non-homologous end joining or homologous recombination (HR). Cell cycle stage and DNA end resection are believed to regulate the commitment to HR repair. Here we identify RNF138 as a ubiquitin E3 ligase that regulates the HR pathway. RNF138 is recruited to DNA damage sites through zinc fingers that have a strong preference for DNA with 5'- or 3'-single-stranded overhangs. RNF138 stimulates DNA end resection and promotes ATR-dependent signalling and DSB repair by HR, thereby contributing to cell survival on exposure to DSB-inducing agents. Finally, we establish that RNF138-dependent Ku removal from DNA breaks is one mechanism whereby RNF138 can promote HR. These results establish RNF138 as an important regulator of DSB repair pathway choice.