Mechanism of Error-Free Bypass of the Environmental Carcinogen N-(2'-Deoxyguanosin-8-yl)-3-aminobenzanthrone Adduct by Human DNA Polymeraseâ
η.
Chembiochem
; 17(21): 2033-2037, 2016 11 03.
Article
en En
| MEDLINE
| ID: mdl-27556902
ABSTRACT
The environmental pollutant 3-nitrobenzanthrone produces bulky aminobenzanthrone (ABA) DNA adducts with both guanine and adenine nucleobases. A major product occurs at the C8 position of guanine (C8-dG-ABA). These adducts present a strong block to replicative polymerases but, remarkably, can be bypassed in a largely error-free manner by the human Y-family polymeraseâ
η (hPol η). Here, we report the crystal structure of a ternary Polâ
DNAâ
dCTP complex between a C8-dG-ABA-containing templateprimer duplex and hPol η. The complex was captured at the insertion stage and provides crucial insight into the mechanism of error-free bypass of this bulky lesion. Specifically, bypass involves accommodation of the ABA moiety inside a hydrophobic cleft to the side of the enzyme active site and formation of an intra-nucleotide hydrogen bond between the phosphate and ABA amino moiety, allowing the adducted guanine to form a standard Watson-Crick pair with the incoming dCTP.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Benzo(a)Antracenos
/
Aductos de ADN
/
Desoxiguanosina
/
ADN Polimerasa Dirigida por ADN
Límite:
Humans
Idioma:
En
Año:
2016
Tipo del documento:
Article