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KMID : 0606920110190030282
Biomolecules & Therapeutics
2011 Volume.19 No. 3 p.282 ~ p.287
Sirt1 Promotes DNA Damage Repair and Cellular Survival
Song Seung-Hyun

Lee Mi-Ok
Lee Ji-Seon
Oh Je-Sok
Cho Sung-Uk
Cha Hyuk-Jin
Abstract
Sirt1, a nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase, is known to deacetylate a number of proteins that are involved in various cellular pathways such as the stress response, apoptosis and cell growth. Modulation of the stress response by Sirtuin 1 (Sirt1) is achieved by the deacetylation of key proteins in a cellular pathway, and leads to a delay in the onset of cancer or aging. In particular, Sirt1 is known to play an important role in maintaining genomic stability, which may be strongly associated with a protective effect during tumorigenesis and during the onset of aging. In these studies, Sirt1 was generated in stably expressing cells and during the stimulation of DNA damage to examine whether it promotes survival. Sirt1 expressing cells facilitated the repair of DNA damage induced by either ionizing radiation (IR) or bleomycin (BLM) treatment. Fastened damaged DNA repair in Sirt1 expressing cells corresponded to prompt activation of Chk2 and ¥ã-H2AX foci formation and promoted survival. Inhibition of Sirt1 enzymatic activity by a chemical inhibitor, nicotinamide (NIC), delayed DNA damage repair, indicating that promoted DNA damage repair by Sirt1 functions to induce survival when DNA damage occurs.
KEYWORD
Sirt1, DNA damage, Ionizing radiation, DNA repair, Radio-chemo sensitizer, Bleomycin
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