Lesion processing: high-fidelity versus lesion-bypass DNA polymerases Journal Article
| Authors: | Broyde, S.; Wang, L.; Rechkoblit, O.; Geacintov, N. E.; Patel, D. J. |
| Article Title: | Lesion processing: high-fidelity versus lesion-bypass DNA polymerases |
| 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. © 2008 Elsevier Ltd. All rights reserved. |
| Keywords: | gene translocation; review; nonhuman; dna polymerase; dna damage; dna repair; structure activity relation; dna; guanine; mismatch repair; protein transport; benzo[a]pyrene; dna structure; benzo(a)pyrene; models, molecular; chemical structure; oxidative stress; sulfolobus solfataricus; 8 hydroxyguanine; dna polymerase beta; dna fragment; crystallography; dna-directed dna polymerase; base pair mismatch; geobacillus stearothermophilus; instrument sterilization; mutagenic activity |
| Journal Title: | Trends in Biochemical Sciences |
| Volume: | 33 |
| Issue: | 5 |
| ISSN: | 0968-0004 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2008-05-01 |
| Start Page: | 209 |
| End Page: | 219 |
| Language: | English |
| DOI: | 10.1016/j.tibs.2008.02.004 |
| PUBMED: | 18407502 |
| PROVIDER: | scopus |
| PMCID: | PMC2717799 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 22" - "Export Date: 17 November 2011" - "CODEN: TBSCD" - "Source: Scopus" |
