| First Author | Nguyen P | Year | 2019 |
| Journal | Radiat Res | Volume | 191 |
| Issue | 5 | Pages | 398-412 |
| PubMed ID | 30835165 | Mgi Jnum | J:318540 |
| Mgi Id | MGI:6860074 | Doi | 10.1667/RR15282.1 |
| Citation | Nguyen P, et al. (2019) Sirt2 Regulates Radiation-Induced Injury. Radiat Res 191(5):398-412 |
| abstractText | 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 gamma-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. |
