FBH1 influences DNA replication fork stability and homologous recombination through ubiquitylation of RAD51
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
FBH1 influences DNA replication fork stability and homologous recombination through ubiquitylation of RAD51. / Chu, Wai Kit; Payne, Miranda J; Beli, Petra; Hanada, Katsuhiro; Choudhary, Chunaram; Hickson, Ian D.
In: Nature Communications, Vol. 6, 5931, 2015.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
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
Y1 - 2015
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
VL - 6
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 5931
ER -
ID: 134708327