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Title: Mechanism of Error-Free Bypass of the Environmental Carcinogen N-(2'-Deoxyguanosin-8-yl)-3-aminobenzanthrone Adduct by Human DNA Polymerase η.

Authors: Patra, Amritraj; Politica, Dustin A; Chatterjee, Arindom; Tokarsky, E John; Suo, Zucai; Basu, Ashis K; Stone, Michael P; Egli, Martin

Published In Chembiochem, (2016 Nov 03)

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 polymerase η (hPol η). Here, we report the crystal structure of a ternary Pol⋅DNA⋅dCTP complex between a C8-dG-ABA-containing template:primer 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.

PubMed ID: 27556902 Exiting the NIEHS site

MeSH Terms: Benz(a)Anthracenes/chemistry; Benz(a)Anthracenes/metabolism*; DNA Adducts/chemistry; DNA Adducts/metabolism*; DNA-Directed DNA Polymerase/chemistry; DNA-Directed DNA Polymerase/metabolism*; Deoxyguanosine/analogs & derivatives*; Deoxyguanosine/chemistry; Deoxyguanosine/metabolism; Humans; Models, Molecular; Molecular Structure

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