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The N-clasp of human DNA polymerase kappa promotes blockage or error-free bypass of adenine- or guanine-benzo[a]pyrenyl lesions.


ABSTRACT: DNA bypass polymerases are utilized to transit bulky DNA lesions during replication, but the process frequently causes mutations. The structural origins of mutagenic versus high fidelity replication in lesion bypass is therefore of fundamental interest. As model systems, we investigated the molecular basis of the experimentally observed essentially faithful bypass of the guanine 10S-(+)-trans-anti-benzo[a]pyrene-N(2)-dG adduct by the Y-family human DNA polymerase kappa, and the observed blockage of pol kappa produced by the adenine 10S-(+)-trans-anti-benzo[a]pyrene-N(2)-dA adduct. These lesions are derived from the most tumorigenic metabolite of the ubiquitous cancer-causing pollutant, benzo[a]pyrene. We compare our results for the dG adduct with our earlier studies for the pol kappa archa

SUBMITTER: Jia L 

PROVIDER: S-EPMC2582633 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature