ZFP161 regulates replication fork stability and maintenance of genomic stability by recruiting the ATR/ATRIP complex

Wootae Kim, Fei Zhao, Rentian Wu, Sisi Qin, Somaira Nowsheen, Jinzhou Huang, Qin Zhou, Yuping Chen, Min Deng, Guijie Guo, Kuntian Luo, Zhenkun Lou () and Jian Yuan ()
Additional contact information
Wootae Kim: Mayo Clinic
Fei Zhao: Mayo Clinic
Rentian Wu: Mayo Clinic
Sisi Qin: Mayo Clinic
Somaira Nowsheen: Mayo Clinic
Jinzhou Huang: Mayo Clinic
Qin Zhou: Mayo Clinic
Yuping Chen: Tongji University School of Medicine
Min Deng: Mayo Clinic
Guijie Guo: Mayo Clinic
Kuntian Luo: Mayo Clinic
Zhenkun Lou: Mayo Clinic
Jian Yuan: Tongji University School of Medicine

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: 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.

Date: 2019
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-019-13321-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13321-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-13321-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().