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.
Mesh Terms:
Animals, Antibodies, Antigens, Surface, Ataxia Telangiectasia Mutated Proteins, Conserved Sequence, DNA Damage, DNA Replication, Gene Expression Regulation, HEK293 Cells, HeLa Cells, Humans, Protein Domains, Rabbits, Stress, Physiological
Animals, Antibodies, Antigens, Surface, Ataxia Telangiectasia Mutated Proteins, Conserved Sequence, DNA Damage, DNA Replication, Gene Expression Regulation, HEK293 Cells, HeLa Cells, Humans, Protein Domains, Rabbits, Stress, Physiological
Curr Biol
Date: Dec. 19, 2016
PubMed ID: 27818175
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