The HLTF–PARP1 interaction in the progression and stability of damaged replication forks caused by methyl methanesulfonate

Jia Lin Shiu, Cheng Kuei Wu, Song Bin Chang, Yan Jhih Sun, Yen Ju Chen, Chien Chen Lai, Wen Tai Chiu, Wen Tsan Chang, Kyungjae Myung, Wen Pin Su, Hungjiun Liaw

研究成果: Article同行評審

1 引文 斯高帕斯(Scopus)

摘要

Human HLTF participates in the lesion-bypass mechanism through the fork reversal structure, known as template switching of post-replication repair. However, the mechanism by which HLTF promotes the replication progression and fork stability of damaged forks remains unclear. Here, we identify a novel protein–protein interaction between HLTF and PARP1. The depletion of HLTF and PARP1 increases chromosome breaks, further reduces the length of replication tracks, and concomitantly increases the number of stalled forks after methyl methanesulfonate treatment according to a DNA fiber analysis. The progression of replication also depends on BARD1 in the presence of MMS treatment. By combining 5-ethynyl-2′-deoxyuridine with a proximity ligation assay, we revealed that the HLTF, PARP1, and BRCA1/BARD1/RAD51 proteins were initially recruited to damaged forks. However, prolonged stalling of damaged forks results in fork collapse. HLTF and PCNA dissociate from the collapsed forks, with increased accumulation of PARP1 and BRCA1/BARD1/RAD51 at the collapsed forks. Our results reveal that HLTF together with PARP1 and BARD1 participates in the stabilization of damaged forks, and the PARP1–BARD1 interaction is further involved in the repair of collapse forks.

原文English
文章編號104
期刊Oncogenesis
9
發行號12
DOIs
出版狀態Published - 2020 12月

All Science Journal Classification (ASJC) codes

  • 分子生物學
  • 癌症研究

指紋

深入研究「The HLTF–PARP1 interaction in the progression and stability of damaged replication forks caused by methyl methanesulfonate」主題。共同形成了獨特的指紋。

引用此