Journal
CELL
Volume 131, Issue 5, Pages 873-886Publisher
CELL PRESS
DOI: 10.1016/j.cell.2007.10.017
Keywords
-
Categories
Ask authors/readers for more resources
Trex1 is the major 3' DNA exonuclease in mammalian cells, and mutations in the human TREX1 gene can cause Aicardi-Goutieres syndrome, characterized by perturbed immunity. Similarly, Trex1(-/-) mice have an autoinflammatory phenotype; however, the mechanism of Trex1-deficient disease is unknown. We report that Trex1, ordinarily associated with the endoplasmic reticulum (ER), relocalizes to the S phase nucleus after gamma irradiation or hydroxyurea treatment. Notably, Trex1-deficient cells show defective G1/S transition and chronic ATM-dependent checkpoint activation, even in the absence of exogenous stress, correlating with persistent single-stranded DNA molecules produced in S phase, which accumulate in the ER. Our data indicate that Trex1 acts on a single-stranded DNA polynucleotide species generated from processing of aberrant replication intermediates to attenuate DNA damage checkpoint signaling and prevent pathological immune activation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available