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

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ZFP161 regulates replication fork stability and maintenance of genomic stability by recruiting the ATR/ATRIP complex.
Nature Communications ( IF 14.7 ) Pub Date : 2019-11-22 , DOI: 10.1038/s41467-019-13321-z
Wootae Kim _{1,

2} , Fei Zhao _{1,

2} , Rentian Wu _{1,

2} , Sisi Qin ₁ , Somaira Nowsheen _{1,

2,

3} , Jinzhou Huang _{1,

2} , Qin Zhou _{1,

2} , Yuping Chen _{4,

5} , Min Deng _{1,

2} , Guijie Guo _{1,

2} , Kuntian Luo _{1,

2} , Zhenkun Lou _{1,

2} , Jian Yuan _{4,

5}

Affiliation

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.

中文翻译：

ZFP161 通过募集 ATR/ATRIP 复合物来调节复制叉的稳定性和基因组稳定性的维持。

DNA 复制应激介导的 ATR 激酶通路激活对于维持基因组稳定性很重要。在这项研究中，我们鉴定了一种锌指蛋白 ZFP161，它在 ATR 激活中充当复制应激反应因子。从机制上讲，ZFP161 充当支架蛋白以促进 RPA 和 ATR/ATRIP 之间的相互作用。ZFP161 通过不同的区域与 RPA 和 ATR/ATRIP 结合，并在停滞的复制叉处稳定 RPA-ATR-ATRIP 复合物。ZFP161 的这一功能对 ATR 信号级联和基因组稳定性维持很重要。此外，ZFP161 基因敲除小鼠表现出 ATR 激活和基因组不稳定性的缺陷。此外，ZFP161 的低表达与较高的癌症风险和染色体不稳定性有关。全面的，

更新日期：2019-11-22

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