Open AccessZFP161 regulates replication fork stability and maintenance of genomic stability by recruiting the ATR/ATRIP complex
Author(s) -
Wootae Kim,
Fei Zhao,
Rentian Wu,
Sisi Qin,
Somaira Nowsheen,
Jinzhou Huang,
Qin Zhou,
Yuping Chen,
Min Deng,
Guijie Guo,
Kuntian Luo,
Zhenkun Lou,
Jian Yuan
Publication year - 2019
Publication title -
nature communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.559
H-Index - 365
ISSN - 2041-1723
DOI - 10.1038/s41467-019-13321-z
Subject(s) - genome instability , dna replication , microbiology and biotechnology , dna damage , minichromosome maintenance , biology , computational biology , genetics , gene , dna , origin of replication
DNA replication stress-mediated activation of the ATR kinase pathway is important for maintaining genomic stability. In this study, we identified a zinc finger protein, ZFP161 that functions as a replication stress response factor in ATR activation. Mechanistically, ZFP161 acts as a scaffolding protein to facilitate the interaction between RPA and ATR/ATRIP. ZFP161 binds to RPA and ATR/ATRIP through distinct regions and stabilizes the RPA–ATR–ATRIP complex at stalled replication forks. This function of ZFP161 is important to the ATR signaling cascade and genome stability maintenance. In addition, ZFP161 knockout mice showed a defect in ATR activation and genomic instability. Furthermore, low expression of ZFP161 is associated with higher cancer risk and chromosomal instability. Overall, these findings suggest that ZFP161 coordinates ATR/Chk1 pathway activation and helps maintain genomic stability.