RNF168 and USP10 regulate topoisomerase IIα function via opposing effects on its ubiquitylation

Research output: Contribution to journalArticlepeer-review


  • Kiran Kumar Naidu Guturi
  • Miyuki Bohgaki
  • Toshiyuki Bohgaki
  • Tharan Srikumar
  • Deborah Ng
  • And 11 others
  • Ramya Kumareswaran
  • Samah El Ghamrasni
  • Justin Jeon
  • Parasvi Patel
  • Mohamed Saad Eldin
  • Rob Bristow
  • Peter Cheung
  • Grant S Stewart
  • Brian Raught
  • Anne Hakem
  • Razqallah Hakem

External organisations

  • University Health Network, Toronto


Topoisomerase IIα (TOP2α) is essential for chromosomal condensation and segregation, as well as genomic integrity. Here we report that RNF168, an E3 ligase mutated in the human RIDDLE syndrome, interacts with TOP2α and mediates its ubiquitylation. RNF168 deficiency impairs decatenation activity of TOP2α and promotes mitotic abnormalities and defective chromosomal segregation. Our data also indicate that RNF168 deficiency, including in human breast cancer cell lines, confers resistance to the anti-cancer drug and TOP2 inhibitor etoposide. We also identify USP10 as a deubiquitylase that negatively regulates TOP2α ubiquitylation and restrains its chromatin association. These findings provide a mechanistic link between the RNF168/USP10 axis and TOP2α ubiquitylation and function, and suggest a role for RNF168 in the response to anti-cancer chemotherapeutics that target TOP2.


Original languageEnglish
Pages (from-to)12638
JournalNature Communications
Early online date25 Aug 2016
Publication statusE-pub ahead of print - 25 Aug 2016

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