Abstract:
:The ATR checkpoint kinase coordinates cellular responses to DNA replication stress. Budding yeast contain three activators of Mec1 (the ATR orthologue); however, only TOPBP1 is known to activate ATR in vertebrates. We identified ETAA1 as a replication stress response protein in two proteomic screens. ETAA1-deficient cells accumulate double-strand breaks, sister chromatid exchanges, and other hallmarks of genome instability. They are also hypersensitive to replication stress and have increased frequencies of replication fork collapse. ETAA1 contains two RPA-interaction motifs that localize ETAA1 to stalled replication forks. It also interacts with several DNA damage response proteins including the BLM/TOP3α/RMI1/RMI2 and ATR/ATRIP complexes. It binds ATR/ATRIP directly using a motif with sequence similarity to the TOPBP1 ATR-activation domain; and like TOPBP1, ETAA1 acts as a direct ATR activator. ETAA1 functions in parallel to the TOPBP1/RAD9/HUS1/RAD1 pathway to regulate ATR and maintain genome stability. Thus, vertebrate cells contain at least two ATR-activating proteins.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Bass TE,Luzwick JW,Kavanaugh G,Carroll C,Dungrawala H,Glick GG,Feldkamp MD,Putney R,Chazin WJ,Cortez Ddoi
10.1038/ncb3415subject
Has Abstractpub_date
2016-11-01 00:00:00pages
1185-1195issue
11eissn
1465-7392issn
1476-4679pii
ncb3415journal_volume
18pub_type
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