RT Journal Article
SR Electronic
T1 PARP1 and PARP2 stabilise replication forks at base excision repair intermediates through Fbh1-dependent Rad51 regulation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 243071
DO 10.1101/243071
A1 George E. Ronson
A1 Ann Liza Piberger
A1 Martin R. Higgs
A1 Anna L. Olsen
A1 Grant S. Stewart
A1 Peter J. McHugh
A1 Eva Petermann
A1 Nicholas D. Lakin
YR 2018
UL http://biorxiv.org/content/early/2018/01/04/243071.abstract
AB PARP1 regulates the repair of DNA single strand breaks (SSBs) generated directly, or during base excision repair (BER). However, the role of PARP2 in these and other repair mechanisms is unknown. Here, we report a requirement for PARP2 in stabilising replication forks that encounter BER intermediates through Fbh1-dependent regulation of Rad51. Whilst PARP2 is dispensable for tolerance of cells to SSBs or homologous recombination dysfunction, it is redundant with PARP1 in BER. Therefore, combined disruption of PARP1 and PARP2 leads to defective BER, resulting in elevated levels of replication associated DNA damage due to an inability to stabilise Rad51 at damaged replication forks and prevent uncontrolled DNA resection. Together, our results demonstrate how PARP1 and PARP2 regulate two independent, but intrinsically linked aspects of DNA base damage tolerance by promoting BER directly, and through stabilising replication forks that encounter BER intermediates.