Jaemin Jeong^1,2, Kyungmi Juhn¹, Hansoo Lee², Sang-Hoon Kim³, Bon-Hong Min⁴, Kyung-Mi Lee⁵, Myung-Haeng Cho⁶, Gil-Hong Park^5,7 and Kee-Ho Lee^1,7

¹Laboratory of Molecular Oncology Korea Institute of Radiological and Medical Sciences Seoul 139-706, Korea
²Vascular System Research Center Division of Life Sciences College of Natural Sciences Kangwon National University Chunchon 200-701, Korea
³Department of Biology Research Institute for Basic Sciences Kyung Hee University Seoul 130-701, Korea
⁴Department of Pharmacology and BK21 Program for Medical Sciences
⁵Department of Biochemistry and Division of BK 21 Program for Biomedical Science Korea University College of Medicine Seoul 136-701, Korea
⁶Laboratory of Toxicology College of Veterinary Medicine Seoul National University Seoul 151-742, Korea
⁷Corresponding authors

Abstract

Human SIRT1 controls various physiological responses including cell fate, stress, and aging, through deacetylation of its specific substrate protein. In processing DNA damage signaling, SIRT1 attenuates a cellular apoptotic response by deacetylation of p53 tumor suppressor. The present study shows that, upon exposure to radiation, SIRT1 could enhance DNA repair capacity and deacetylation of repair protein Ku70. Ectopically over-expressed SIRT1 resulted in the increase of repair of DNA strand breakages produced by radiation. On the other hand, repression of endogenous SIRT1 expression by SIRT1 siRNA led to the decrease of this repair activity, indicating that SIRT1 can regulate DNA repair capacity of cells with DNA strand breaks. In addition, we found that SIRT1 physically complexed with repair protein Ku70, leading to subsequent deacetylation. The dominant-negative SIRT1, a catalytically inactive form, did not induce deacetylation of Ku70 protein as well as increase of DNA repair capacity. These observations suggest that SIRT1 modulates DNA repair activity, which could be regulated by the acetylation status of repair protein Ku70 following DNA damage.

Keywords: DNA damage; DNA repair; Ku autoantigen; radiation, ionizing; SIRT1 protein, human