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

TY - JOUR

T1 - FBH1 influences DNA replication fork stability and homologous recombination through ubiquitylation of RAD51

AU - Chu, Wai Kit

AU - Payne, Miranda J

AU - Beli, Petra

AU - Hanada, Katsuhiro

AU - Choudhary, Chunaram

AU - Hickson, Ian D

PY - 2015/1

Y1 - 2015/1

N2 - 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 SCF(FBH1) 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.

AB - 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 SCF(FBH1) 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.

U2 - 10.1038/ncomms6931

DO - 10.1038/ncomms6931

M3 - Journal article

C2 - 25585578

SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

M1 - 5931

ER -