Exploring damage recognition models in prokaryotic nucleotide excision repair with a benzo[a]pyrene-derived lesion in UvrB

Lei Jia, Konstantin Kropachev, Shuang Ding, Bennett Van Houten, Nicholas E. Geacintov, Suse Broyde

Research output: Contribution to journalArticle

Abstract

The UvrB protein is a central unit for damage recognition in the prokaryotic nucleotide excision repair system, which excises bulky DNA lesions. We have utilized molecular modeling and MD simulations based on crystal structures, mutagenesis, and fluorescence data, to model the 10R-(+)-cis-anti-B[a]P-N2-dG lesion, derived from the tumorigenic (+)-anti-B[a]PDE metabolite of benzo[a]pyrene, at different locations on the inner and outer strand in UvrB. Our results suggest that this lesion is accommodated on the inner strand where it might translocate through the tunnel created by the β-hairpin and UvrB domain 1B and ultimately could be housed in the pocket behind the β-hairpin prior to excision by UvrC. Lesions that vary in size and shape may be stopped at the gate to the tunnel, within the tunnel, or in the pocket when UvrC initiates excision. Common features of β-hairpin intrusion between the two DNA strands and nucleotide flipping manifested in structures of prokaryotic and eukaryotic NER lesion recognition proteins are consistent with common recognition mechanisms, based on lesion-induced local thermodynamic distortion/destabilization and nucleotide flipping.

Original languageEnglish (US)
Pages (from-to)8948-8957
Number of pages10
JournalBiochemistry
Volume48
Issue number38
DOIs
StatePublished - 2009

ASJC Scopus subject areas

  • Biochemistry

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