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Molecular and Cellular Biology, March 2006, p. 1654-1665, Vol. 26, No. 5
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.5.1654-1665.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Acetylation of Human 8-Oxoguanine-DNA Glycosylase by p300 and Its Role in 8-Oxoguanine Repair In Vivo

Kishor K. Bhakat,1,{dagger} Sanath K. Mokkapati,1,{dagger} Istvan Boldogh,2 Tapas K. Hazra,1 and Sankar Mitra1*

Sealy Center for Molecular Science and Department of Human Biological Chemistry and Genetics,1 Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas 775552

Received 1 March 2005/ Returned for modification 27 March 2005/ Accepted 8 December 2005

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 (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 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.

* Corresponding author. Mailing address: Sealy Center for Molecular Science, University of Texas Medical Branch, 6.136 Medical Research Building, Route 1079, Galveston, TX 77555. Phone: (409) 772-1780. Fax: (409) 747-8608. E-mail: samitra{at}utmb.edu.

{dagger} Contributed equally to this work.

Molecular and Cellular Biology, March 2006, p. 1654-1665, Vol. 26, No. 5
0022-538X/06/$08.00+0     doi:10.1128/MCB.26.5.1654-1665.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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