Lesion processing: high-fidelity versus lesion-bypass DNA polymerases.
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.
Broyde
Suse
S
Department of Biology, New York University, 100 Washington Square East, 1009 Silver Center, New York, NY 10003, USA. broyde@nyu.edu <broyde@nyu.edu>
Wang
Lihua
L
Rechkoblit
Olga
O
Geacintov
Nicholas E
NE
Patel
Dinshaw J
DJ
D020137:Base Pair Mismatch; D001564:Benzo(a)pyrene / Q000494:pharmacology; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D019951:DNA Polymerase beta / Q000502:physiology; D004260:DNA Repair / Q000502:physiology*; D004259:DNA-Directed DNA Polymerase / Q000502:physiology*; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D008958:Models, Molecular; D021381:Protein Transport; D048229:Sulfolobus solfataricus / Q000201:enzymology
C453560:7,8-dihydro-8-oxoguanine; D001564:Benzo(a)pyrene; D006147:Guanine; D004247:DNA; D019951:DNA Polymerase beta; D004259:DNA-Directed DNA Polymerase