Lesion processing: high-fidelity versus lesion-bypass DNA polymerases

Suse Broyde, Lihua Wang, Olga Rechkoblit, Nicholas E. Geacintov, Dinshaw J. Patel

Research output: Contribution to journalReview article

Abstract

When a high-fidelity DNA polymerase encounters certain DNA-damage sites, its progress can be stalled and one or more lesion-bypass polymerases are recruited to transit the lesion. Here, we consider two representative types of lesions: (i) 7,8-dihydro-8-oxoguanine (8-oxoG), a small, highly prevalent lesion caused by oxidative damage; and (ii) bulky lesions derived from the environmental pre-carcinogen benzo[a]pyrene, in the high-fidelity DNA polymerase Bacillus fragment (BF) from Bacillus stearothermophilus and in the lesion-bypass DNA polymerase IV (Dpo4) from Sulfolobus solfataricus. The tight fit of the BF polymerase around the nascent base pair contrasts with the more spacious, solvent-exposed active site of Dpo4, and these differences in architecture result in distinctions in their respective functions: one-step versus stepwise polymerase translocation, mutagenic versus accurate bypass of 8-oxoG, and polymerase stalling versus mutagenic bypass at bulky benzo[a]pyrene-derived lesions.

Original languageEnglish (US)
Pages (from-to)209-219
Number of pages11
JournalTrends in Biochemical Sciences
Volume33
Issue number5
DOIs
StatePublished - May 2008

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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