Physical interaction of RECQ5 helicase with RAD51 facilitates its anti-recombinase activity

Sybille Schwendener, Steven Raynard, Shreya Paliwal, Anita Cheng, Radhakrishnan Kanagaraj, Igor Shevelev, Jeremy M. Stark, Patrick Sung, Pavel Janscak

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

Homologous recombination (HR) provides an efficient mechanism for error-free repair of DNA double-strand breaks (DSBs). However, HR can be also harmful as inappropriate or untimely HR events can give rise to lethal recombination intermediates and chromosome rearrangements. A critical step of HR is the formation of a RAD51 filament on single-stranded (ss)DNA, which mediates the invasion of a homologous DNA molecule. In mammalian cells, several DNA helicases have been implicated in the regulation of this process. RECQ5, a member of the RecQ family of DNA helicases, interacts physically with the RAD51 recombinase and disrupts RAD51 presynaptic filaments in a reaction dependent on ATP hydrolysis. Here, we have precisely mapped the RAD51-interacting domain of RECQ5 and generated mutants that fail to interact with RAD51. We show that although these mutants retain normal ATPase activity, they are impaired in their ability to displace RAD51 from ssDNA. Moreover, we show that ablation of RECQ5-RAD51 complex formation by a point mutation alleviates the inhibitory effect of RECQ5 on HR-mediated DSB repair. These findings provide support for the proposal that interaction with RAD51 is critical for the anti-recombinase attribute of RECQ5.

Original languageEnglish (US)
Pages (from-to)15739-15745
Number of pages7
JournalJournal of Biological Chemistry
Volume285
Issue number21
DOIs
StatePublished - May 21 2010
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Schwendener, S., Raynard, S., Paliwal, S., Cheng, A., Kanagaraj, R., Shevelev, I., Stark, J. M., Sung, P., & Janscak, P. (2010). Physical interaction of RECQ5 helicase with RAD51 facilitates its anti-recombinase activity. Journal of Biological Chemistry, 285(21), 15739-15745. https://doi.org/10.1074/jbc.M110.110478