PARP1 recruits DNA translocases to restrain DNA replication and facilitate DNA repair

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, Peter Chi, Hungjiun Liaw

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

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.

Original languageEnglish
Article numbere1010545
JournalPLoS genetics
Volume18
Issue number12
DOIs
Publication statusPublished - 2022 Dec 13

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

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