RPA-Binding Protein ETAA1 Is an ATR Activator Involved in DNA Replication Stress Response

被引：110

作者：

Lee, Yuan-Cho ^{[1
]}

Zhou, Qing ^{[1
]}

Chen, Junjie ^{[2
]}

Yuan, Jingsong ^{[1
]}

机构：

[1] Columbia Univ, Dept Radiat Oncol, Ctr Radiol Res, Med Ctr, 630 West 168th St,New, New York, NY 10032 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Expt Radiat Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA

来源：

CURRENT BIOLOGY | 2016年 / 26卷 / 24期

关键词：

A RPA; STRANDED DNA; CHECKPOINT; DAMAGE; TOPBP1; CHK1; HELICASE; COMPLEX; KINASE; SSDNA;

D O I：

10.1016/j.cub.2016.10.030

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

ETAA1 (Ewing tumor-associated antigen 1), also known as ETAA16, was identified as a tumor-specific antigen in the Ewing family of tumors. However, the biological function of this protein remains unknown. Here, we report the identification of ETAA1 as a DNA replication stress response protein. ETAA1 specifically interacts with RPA (Replication protein A) via two conserved RPA-binding domains and is therefore recruited to stalled replication forks. Interestingly, further analysis of ETAA1 function revealed that ETAA1 participates in the activation of ATR signaling pathway via a conserved ATR-activating domain (AAD) located near its N terminus. Importantly, we demonstrate that both RPA binding and ATR activation are required for ETAA1 function at stalled replication forks tomaintain genome stability. Therefore, our data suggest that ETAA1 is a new ATR activator involved in replication checkpoint control.

引用

页码：3257 / 3268

页数：12

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