Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Sirt1 Promotes DNA Damage Repair and Cellular Survival

  • Song, Seung-Hyun (Department of Biomedical Science, CHA University) ;
  • Lee, Mi-Ok (Department of Biomedical Science, CHA University) ;
  • Lee, Ji-Seon (Department of Life Sciences, College of Natural Sciences, Sogang University) ;
  • Oh, Je-Sok (Department of Biotechnology and Environmental Engineering, Catholic University) ;
  • Cho, Sung-Uk (Department of Biomedical Science, CHA University) ;
  • Cha, Hyuk-Jin (Department of Life Sciences, College of Natural Sciences, Sogang University)
  • Received : 2011.05.21
  • Accepted : 2011.06.08
  • Published : 2011.07.31
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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 ${\gamma}$-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.

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References

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