ZFP161 regulates replication fork stability and maintenance of genomic stability by recruiting the ATR/ATRIP complex.
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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Ataxia Telangiectasia Mutated Proteins, Checkpoint Kinase 1, DNA Damage, DNA Replication, DNA-Binding Proteins, Genomic Instability, HEK293 Cells, Humans, Kruppel-Like Transcription Factors, Mice, Mice, Knockout, Replication Protein A, Repressor Proteins, Signal Transduction
Adaptor Proteins, Signal Transducing, Animals, Ataxia Telangiectasia Mutated Proteins, Checkpoint Kinase 1, DNA Damage, DNA Replication, DNA-Binding Proteins, Genomic Instability, HEK293 Cells, Humans, Kruppel-Like Transcription Factors, Mice, Mice, Knockout, Replication Protein A, Repressor Proteins, Signal Transduction
Nat Commun
Date: Dec. 22, 2018
PubMed ID: 31757956
View in: Pubmed Google Scholar
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