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FBH1 influences DNA replication fork stability and homologous recombination through ubiquitylation of RAD51

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  • Wai Kit Chu

    (Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital
    Center for Healthy Aging, Panum Institute, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark)

  • Miranda J. Payne

    (Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital)

  • Petra Beli

    (Novo Nordisk Foundation Center for Protein Research, University of Copenhagen)

  • Katsuhiro Hanada

    (Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital)

  • Chunaram Choudhary

    (Novo Nordisk Foundation Center for Protein Research, University of Copenhagen)

  • Ian D. Hickson

    (Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital
    Center for Healthy Aging, Panum Institute, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark)

Abstract

Unscheduled homologous recombination (HR) can lead to genomic instability, which greatly increases the threat of neoplastic transformation in humans. The F-box DNA helicase 1 (FBH1) is a 3′–5′ DNA helicase with a putative function as a negative regulator of HR. It is the only known DNA helicase to contain an F-box, suggesting that one of its functions is to act as a ubiquitin ligase as part of an SCF (SKP1, CUL1 and F-box) complex. Here we report that the central player in HR, RAD51, is ubiquitylated by the SCFFBH1 complex. Expression of an ubiquitylation-resistant form of RAD51 in human cells leads to hyperrecombination, as well as several phenotypes indicative of an altered response to DNA replication stress. These effects are likely to be mediated by the enhanced nuclear matrix association of the ubiquitylation-resistant RAD51. These data are consistent with FBH1 acting as a negative regulator of RAD51 function in human cells.

Suggested Citation

  • Wai Kit Chu & Miranda J. Payne & Petra Beli & Katsuhiro Hanada & Chunaram Choudhary & Ian D. Hickson, 2015. "FBH1 influences DNA replication fork stability and homologous recombination through ubiquitylation of RAD51," Nature Communications, Nature, vol. 6(1), pages 1-9, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms6931
    DOI: 10.1038/ncomms6931
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