Acetylation of human 8-oxoguanine-DNA glycosylase by p300 and its role in 8-oxoguanine repair in vivo

Kishor K. Bhakat, Sanath K. Mokkapati, Istvan Boldogh, Tapas Hazra, Sankar Mitra

Research output: Contribution to journalArticle

117 Citations (Scopus)

Abstract

The human 8-oxoguanine-DNA glycosylase 1 (OGG1) is the major DNA glycosylase responsible for repair of 7,8-slihydro-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 (AP) site product. The enhanced rate of repair of 8-oxoG in the genome by wild-type OGG1 but not the K338R/K341R mutant, ectopically expressed in oxidatively stressed OGG1-null mouse embryonic fibroblasts, suggests that acctylation 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.

Original languageEnglish (US)
Pages (from-to)1654-1665
Number of pages12
JournalMolecular and Cellular Biology
Volume26
Issue number5
DOIs
StatePublished - Mar 2006

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DNA Glycosylases
Acetylation
DNA-(Apurinic or Apyrimidinic Site) Lyase
Histone Deacetylases
human oxoguanine glycosylase 1
8-hydroxyguanine
HeLa Cells
Reactive Oxygen Species
Oxidative Stress
Fibroblasts
Genome
Peptides
DNA

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Acetylation of human 8-oxoguanine-DNA glycosylase by p300 and its role in 8-oxoguanine repair in vivo. / Bhakat, Kishor K.; Mokkapati, Sanath K.; Boldogh, Istvan; Hazra, Tapas; Mitra, Sankar.

In: Molecular and Cellular Biology, Vol. 26, No. 5, 03.2006, p. 1654-1665.

Research output: Contribution to journalArticle

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