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

Wai Kit Chu, Miranda J. Payne, Petra Beli, Katsuhiro Hanada, Chunaram Choudhary and Ian D. Hickson ()
Additional contact information
Wai Kit Chu: Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital
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

Nature Communications, 2015, vol. 6, issue 1, 1-9

Abstract: 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.

Date: 2015
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms6931 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms6931

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms6931

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().