Efficient removal of formamidopyrimidines by 8-oxoguanine glycosylases

Nirmala Krishnamurthy, Kazuhiro Haraguchi, Marc M. Greenberg, Sheila S. David

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Under conditions of oxidative stress, the formamidopyrimidine lesions (FapyG and FapyA) are formed in competition with the corresponding 8-oxopurines (OG and OA) from a common intermediate. In order to reveal features of the repair of these lesions, and the potential contribution of repair in mitigating or exacerbating the mutagenic properties of Fapy lesions, their excision by three glycosylases, Fpg, hOGG1 and Ntg1, was examined in various base pair contexts under single-turnover conditions. FapyG was removed at least as efficiently as OG by all three glycosylases. In addition, the rates of removal of FapyG by Fpg and hOGG1 were influenced by their base pair partner, with preference for removal when base paired with the correct Watson-Crick partner C. With the FapyA lesion, Fpg and Ntg1 catalyze its removal more readily than OG opposite all four natural bases. In contrast, the removal of FapyA by hOGG1 was not as robust as FapyG or OG, and was only significant when the lesion was paired with C. The discrimination by the various glycosylases with respect to the opposing base was highly dependent on the identity of the lesion. OG induced the greatest selectivity against its removal when part of a promutagenic base pair. The superb activity of the various OG glycosylases toward removal of FapyG and FapyA in vitro suggests that these enzymes may act upon these oxidized lesions in vivo. The differences in the activity of the various glycosylases for removal of FapyG and FapyA compared to OG in nonmutagenic versus promutagenic base pair contexts may serve to alter the mutagenic profiles of these lesions in vivo.

Original languageEnglish (US)
Pages (from-to)1043-1050
Number of pages8
JournalBiochemistry
Volume47
Issue number3
DOIs
StatePublished - Jan 22 2008

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Base Pairing
Purinones
Repair
Oxidative Stress
Oxidative stress
8-hydroxyguanine
Enzymes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Krishnamurthy, N., Haraguchi, K., Greenberg, M. M., & David, S. S. (2008). Efficient removal of formamidopyrimidines by 8-oxoguanine glycosylases. Biochemistry, 47(3), 1043-1050. https://doi.org/10.1021/bi701619u

Efficient removal of formamidopyrimidines by 8-oxoguanine glycosylases. / Krishnamurthy, Nirmala; Haraguchi, Kazuhiro; Greenberg, Marc M.; David, Sheila S.

In: Biochemistry, Vol. 47, No. 3, 22.01.2008, p. 1043-1050.

Research output: Contribution to journalArticle

Krishnamurthy, N, Haraguchi, K, Greenberg, MM & David, SS 2008, 'Efficient removal of formamidopyrimidines by 8-oxoguanine glycosylases', Biochemistry, vol. 47, no. 3, pp. 1043-1050. https://doi.org/10.1021/bi701619u
Krishnamurthy N, Haraguchi K, Greenberg MM, David SS. Efficient removal of formamidopyrimidines by 8-oxoguanine glycosylases. Biochemistry. 2008 Jan 22;47(3):1043-1050. https://doi.org/10.1021/bi701619u
Krishnamurthy, Nirmala ; Haraguchi, Kazuhiro ; Greenberg, Marc M. ; David, Sheila S. / Efficient removal of formamidopyrimidines by 8-oxoguanine glycosylases. In: Biochemistry. 2008 ; Vol. 47, No. 3. pp. 1043-1050.
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