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

RPA-Binding Protein ETAA1 Is an ATR Activator Involved in DNA Replication Stress Response 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 to maintain genome stability. Therefore, our data suggest that ETAA1 is a new ATR activator involved in replication checkpoint control. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Current Biology Elsevier

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

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Publisher
Cell Press
Copyright
Copyright © 2016 Elsevier Ltd
ISSN
0960-9822
D.O.I.
10.1016/j.cub.2016.10.030
Publisher site
See Article on Publisher Site

Abstract

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 to maintain genome stability. Therefore, our data suggest that ETAA1 is a new ATR activator involved in replication checkpoint control.

Journal

Current BiologyElsevier

Published: Dec 19, 2016

References

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