Repair of Oxidized Bases in DNA Bubble Structures by Human DNA Glycosylases NEIL1 and NEIL2

Hong Dou, Sankar Mitra, Tapas K. Hazra

Research output: Contribution to journalArticle

260 Scopus citations

Abstract

Repair of oxidatively damaged bases in the genome via the base excision repair pathway is initiated with excision of these lesions by DNA glycosylases with broad substrate range. The newly discovered human DNA glycosylases, NEIL1 and NEIL2, are distinct in structural features and reaction mechanism from the previously characterized NTH1 and OGG1 but act on many of the same substrates. However, NEIL2 shows a unique preference for excising lesions from a DNA bubble, whereas NTH1 and OGG1 are only active with duplex DNA. NEIL1 also excises efficiently 5-hydroxyuracil, an oxidation product of cytosine, from the bubble and single-stranded DNA but does not have strong activity toward 8-oxoguanine in the bubble. The dichotomy in the activity of NEILs versus NTH1/OGG1 for bubble versus duplex DNA substrates is consistent with higher affinity of the NEILs for the bubble structures of both damaged and undamaged DNA relative to duplex structure. These observations suggest that the NEILs are functionally distinct from OGG1/NTH1 in vivo. OGG1/NTH1-independent repair of oxidized bases in the transcribed sequences supports the possibility that NEILs are preferentially involved in repair of lesions in DNA bubbles generated during transcription and/or replication.

Original languageEnglish (US)
Pages (from-to)49679-49684
Number of pages6
JournalJournal of Biological Chemistry
Volume278
Issue number50
DOIs
StatePublished - Dec 12 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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