We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
The HINT1 tumor suppressor regulates both γ-H2AX and ATM in response to DNA damage.
- Authors
Li, Haiyang; Balajee, Adayabalam S.; Tao Su; Cen, Bo; Hei, Tom K.; Weinstein, I. Bernard
- Abstract
Hint1 is a haploinsufficient tumor suppressor gene and the underlying molecular mechanisms for its tumor suppressor function are unknown. In this study we demonstrate that HINT1 participates in ionizing radiation (IR)-induced DNA damage responses. In response to IR, HINT1 is recruited to IR-induced foci (IRIF) and associates with γ-H2AX and ATM. HINT1 deficiency does not affect the formation of γ-H2AX foci; however, it impairs the removal of γ-H2AX foci after DNA damage and this is associated with impaired acetylation of γ-H2AX. HINT1 deficiency also impairs acetylation of ATM and activation of ATM and its downstream effectors, and retards DNA repair, in response to IR. HINT1-deficient cells exhibit resistance to IR-induced apoptosis and several types of chromosomal abnormalities. Our findings suggest that the tumor suppressor function of HINT1 is caused by, at least in part, its normal role in enhancing cellular responses to DNA damage by regulating the functions of both γ-H2AX and ATM.
- Subjects
TUMOR suppressor genes; GENETIC regulation; DNA damage; IONIZING radiation; ACETYLATION; DNA repair; CELL death; CHROMOSOME abnormalities
- Publication
Journal of Cell Biology, 2008, Vol 183, Issue 2, p253
- ISSN
0021-9525
- Publication type
Article
- DOI
10.1083/jcb.200711150