PARP1 recruits DNA translocases to restrain DNA replication and facilitate DNA repair
Journal
PLOS Genetics
Journal Volume
18
Journal Issue
12
ISSN
1553-7404
Date Issued
2022-12-13
Author(s)
Yen-Chih Ho
Chen-Syun Ku
Siang-Sheng Tsai
Jia-Lin Shiu
Yi-Zhen Jiang
Hui Emmanuela Miriam
Han-Wen Zhang
Yen-Tzu Chen
Wen-Tai Chiu
Song-Bin Chang
Che-Hung Shen
Kyungjae Myung
Hungjiun Liaw
Abstract
Replication fork reversal which restrains DNA replication progression is an important protective mechanism in response to replication stress. PARP1 is recruited to stalled forks to restrain DNA replication. However, PARP1 has no helicase activity, and the mechanism through which PARP1 participates in DNA replication restraint remains unclear. Here, we found novel protein-protein interactions between PARP1 and DNA translocases, including HLTF, SHPRH, ZRANB3, and SMARCAL1, with HLTF showing the strongest interaction among these DNA translocases. Although HLTF and SHPRH share structural and functional similarity, it remains unclear whether SHPRH contains DNA translocase activity. We further identified the ability of SHPRH to restrain DNA replication upon replication stress, indicating that SHPRH itself could be a DNA translocase or a helper to facilitate DNA trans-location. Although hydroxyurea (HU) and MMS induce different types of replication stress, they both induce common DNA replication restraint mechanisms independent of intra-S phase activation. Our results suggest that the PARP1 facilitates DNA translocase recruitment to damaged forks, preventing fork collapse and facilitating DNA repair.
SDGs
Publisher
Public Library of Science (PLoS)
Description
Article number e1010545
Type
journal article