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

• Author(s) / Creator(s)

  • Ismail Hassan Ismail1,2*, Jean-Philippe Gagné3, Marie-Michelle Genois3, 4, Hilmar Strickfaden1, Darin McDonald1, Zhizhong Xu1, Guy G Poirier3 , Jean-Yves Masson3, 4 and Michael J Hendzel1,

• DNA double-strand breaks (DSBs) are repaired mainly by non-homologous end
  joining (NHEJ) 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 an 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 upon exposure to DSBinducing 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.

• Date created

  2015-01-01

• Subjects / Keywords

  • DNA REPAIR
  • DOUBLE-STRAND BREAK
  • HOMOLOGOUS RECOMBINATION REPAIR
  • NONHOMOLOGOUS END JOINING
  • KU

• Type of Item

  Article (Published)

• DOI

  https://doi.org/10.7939/r3-58av-z061

• License

  Attribution-NonCommercial 4.0 International