Stimulation of DNA glycosylase activity of OGG1 by NEIL1: Functional collaboration between two human DNA glycosylases

Sanath K. Mokkapati, Lee Wiederhold, Tapas Hazra, Sankar Mitra

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

The eukaryotic 8-oxoguanine-DNA glycosylase 1 (OGG1) provides the major activity for repairing mutagenic 7,8-dihydro-8-oxoguanine (8-oxoG) induced in the genome due to oxidative stress. Earlier in vitro studies showed that, after excising the base lesion, the human OGG1 remains bound to the resulting abasic (AP) site in DNA and does not turn over efficiently. The human AP-endonuclease (APE1), which cleaves the phosphodiester bond 5′ to the AP site, in the next step of repair, displaces the bound OGG1 and thus increases its turnover. Here we show that NEIL1, a DNA glycosylase/AP lyase specific for many oxidized bases but with weak 8-oxoG excision activity, stimulates turnover of OGG1 in a fashion similar to that of APE1 and carries out βδ-elimination at the AP site. This novel collaboration of two DNA glycosylases, which do not stably interact with each other, in stimulating 8-oxoguanine repair is possible because of higher AP site affinity and stronger AP lyase activity of NEIL1 relative to OGG1. Comparable levels of NEIL1 and OGG1 in some human cells raise the possibility that NEIL1 serves as a backup enzyme to APE1 in stimulating 8-oxoG repair in vivo.

Original languageEnglish (US)
Pages (from-to)11596-11604
Number of pages9
JournalBiochemistry
Volume43
Issue number36
DOIs
StatePublished - Sep 14 2004

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DNA Glycosylases
DNA-(Apurinic or Apyrimidinic Site) Lyase
Repair
Oxidative stress
8-hydroxyguanine
Oxidative Stress
Genes
Cells
Genome
DNA
Enzymes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Stimulation of DNA glycosylase activity of OGG1 by NEIL1 : Functional collaboration between two human DNA glycosylases. / Mokkapati, Sanath K.; Wiederhold, Lee; Hazra, Tapas; Mitra, Sankar.

In: Biochemistry, Vol. 43, No. 36, 14.09.2004, p. 11596-11604.

Research output: Contribution to journalArticle

Mokkapati, Sanath K. ; Wiederhold, Lee ; Hazra, Tapas ; Mitra, Sankar. / Stimulation of DNA glycosylase activity of OGG1 by NEIL1 : Functional collaboration between two human DNA glycosylases. In: Biochemistry. 2004 ; Vol. 43, No. 36. pp. 11596-11604.
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