| First Author | Kim W | Year | 2019 |
| Journal | Nat Commun | Volume | 10 |
| Issue | 1 | Pages | 5304 |
| PubMed ID | 31757956 | Mgi Jnum | J:284769 |
| Mgi Id | MGI:6387610 | Doi | 10.1038/s41467-019-13321-z |
| Citation | Kim W, et al. (2019) ZFP161 regulates replication fork stability and maintenance of genomic stability by recruiting the ATR/ATRIP complex. Nat Commun 10(1):5304 |
| abstractText | 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. |
