ZFP161 regulates replication fork stability and maintenance of genomic stability by recruiting the ATR/ATRIP complex.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31757956.
- Also identified by DOI 10.1038/s41467-019-13321-z and PMC identifier 6876566.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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.
Medical subject headings
- Adaptor Proteins, Signal Transducing
- Ataxia Telangiectasia Mutated Proteins
- DNA-Binding Proteins
- Genomic Instability
- Kruppel-Like Transcription Factors
- Repressor Proteins