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5 March 2019 Sirt2 Regulates Radiation-Induced Injury
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Nguyen, P., Shukla, S., Liu, R., Abbineni, G. and Smart, D. K. Sirt2 Regulates Radiation-Induced Injury. Radiat. Res. 191, 398–412 (2019).

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.

©2019 by Radiation Research Society. All rights of reproduction in any form reserved.
Phuongmai Nguyen, Sudhanshu Shukla, Ryan Liu, Gopal Abbineni, and DeeDee K. Smart "Sirt2 Regulates Radiation-Induced Injury," Radiation Research 191(5), 398-412, (5 March 2019).
Received: 30 October 2018; Accepted: 11 February 2019; Published: 5 March 2019

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