期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 26, 期 5, 页码 1654-1665出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.26.5.1654-1665.2006
关键词
-
资金
- NCI NIH HHS [R01 CA 81063, R01 CA053791, R01 CA53791, R01 CA081063] Funding Source: Medline
- NIA NIH HHS [P01 AG021830] Funding Source: Medline
- NIEHS NIH HHS [P30 ES006676, P50 ES 06676] Funding Source: Medline
The human 8-oxoguanine-DNA glycosylase 1 (OGG1) is the major DNA glycosylase responsible for repair of 7,8-dihydro-8-oxoguanine (8-oxoG) and ring-opened fapyguanine, critical mutagenic DNA lesions that are induced by reactive oxygen species. Here we show that OGG1 is acetylated by p300 in vivo predominantly at Lys338/Lys341. About 20% of OGG1 is present in acetylated form in HeLa cells. Acetylation significantly increases OGG1's activity in vitro in the presence of AP-endonuclease by reducing its affinity for the abasic (A-P) site product. The enhanced rate of repair of 8-oxoG in the genome by wild-type OGG1. but not the K338R/K34IR mutant, ectopically expressed in oxidatively stressed OGG1-null mouse embryonic fibroblasts, suggests that acetylation increases OGG1 activity in vivo. At the same time, acetylation of OGG1 was increased by about 2.5-fold after oxidative stress with no change at the polypeptide level. OGG1 interacts with class I histone deacetylases, which may be responsible for its deacetylation. Based on these results, we propose a novel regulatory function of OGG1 acetylation in repair of its substrates in oxidatively stressed cells.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据