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Trends Biochem Sci. 2008 May;33(5):209-19. doi: 10.1016/j.tibs.2008.02.004. Epub 2008 Apr 11.

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

Author information

  • 1Department of Biology, New York University, 100 Washington Square East, 1009 Silver Center, New York, NY 10003, USA. broyde@nyu.edu <broyde@nyu.edu>

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.

PMID:
18407502
PMCID:
PMC2717799
DOI:
10.1016/j.tibs.2008.02.004
[PubMed - indexed for MEDLINE]
Free PMC Article
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