Open AccessSirt2 Regulates Radiation-Induced Injury
Author(s) -
Phuongmai Nguyen,
Sudhanshu Shukla,
Ryan Liu,
Gopal Abbineni,
Dee Dee Smart
Publication year - 2019
Publication title -
radiation research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 124
eISSN - 1938-5404
pISSN - 0033-7587
DOI - 10.1667/rr15282.1
Subject(s) - sirt2 , dna damage , dna repair , biology , sirtuin , microbiology and biotechnology , programmed cell death , carcinogenesis , cancer research , knockout mouse , gene knockdown , cell culture , genetics , dna , gene , apoptosis , acetylation
Sirtuin 2 (SIRT2) plays a major role in aging, carcinogenesis and neurodegeneration. While it has been shown that SIRT2 is a mediator of stress-induced cell death, the mechanism remains unclear. In this study, we report the role of SIRT2 in mediating radiation-induced cell death and DNA damage using mouse embryonic fibroblasts (MEFs), progenitor cells and tissues from Sirt2 wild-type and genomic knockout mice, and human tumor and primary cell lines as models. The presence of Sirt2 in cells and tissues significantly enhanced the cell's sensitivity to radiation-induced cytotoxicity by delaying the dispersion of radiation-induced γ-H2AX and 53BP1 foci. This enhanced cellular radiosensitivity correlated with reduced expression of pro-survival and DNA repair proteins, and decreased DNA repair capacities involving both homologous repair and non-homologous end joining DNA repair mechanisms compared to those in Sirt2 knockout (KO) and knockdown (KD) phenotypes. Together, these data suggest SIRT2 plays a critical role in mediating the radiation-induced DNA damage response, thus regulating radiation-induced cell death and survival.