SIRT1 promotes DNA repair activity and deacetylation of Ku70.
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.
Jeong
Jaemin
J
Laboratory of Molecular Oncology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Korea.
Juhn
Kyungmi
K
Lee
Hansoo
H
Kim
Sang-Hoon
SH
Min
Bon-Hong
BH
Lee
Kyung-Mi
KM
Cho
Myung-Haeng
MH
Park
Gil-Hong
GH
Lee
Kee-Ho
KH
D000107:Acetylation; D034961:Antigens, Nuclear / Q000378:metabolism*; D002460:Cell Line; D004247:DNA / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D000072200:Ku Autoantigen; D034741:RNA, Small Interfering / Q000235:genetics; D056564:Sirtuin 1; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; D004247:DNA; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen