TY - JOUR
T1 - ZFP161 regulates replication fork stability and maintenance of genomic stability by recruiting the ATR/ATRIP complex
AU - Kim, Wootae
AU - Zhao, Fei
AU - Wu, Rentian
AU - Qin, Sisi
AU - Nowsheen, Somaira
AU - Huang, Jinzhou
AU - Zhou, Qin
AU - Chen, Yuping
AU - Deng, Min
AU - Guo, Guijie
AU - Luo, Kuntian
AU - Lou, Zhenkun
AU - Yuan, Jian
N1 - Funding Information:
This research was supported by funding from the Mayo Foundation and Basic Science Research Program through the National Research Foundation of Korea (NRF) (NRF-2018R1A6A3A03012613). We thank Dr. David Cortez, Dr. Lee Zou and Dr. David Yu for ATRIP vectors and Dr. Marc Wold for RPA complex vector.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-019-13321-z
DO - 10.1038/s41467-019-13321-z
M3 - Article
C2 - 31757956
AN - SCOPUS:85075531897
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5304
ER -