The E295K cancer variant of human polymerase β favors the mismatch conformational pathway during nucleotide selection.

ABSTRACT: DNA polymerase β (pol β) is responsible for gap filling synthesis during repair of damaged DNA as part of the base excision repair pathway. Human pol β mutations were recently identified in a high percentage (∼30%) of tumors. Characterization of specific cancer variants is particularly useful to further the understanding of the general mechanism of pol β while providing context to disease contribution. We showed that expression of the carcinoma variant E295K induces cellular transformation. The poor polymerase activity exhibited by the variant was hypothesized to be caused by the destabilization of proper active site assembly by the glutamate to lysine mutation. Here, we show that this variant exhibits an unusual preference for binding dCTP opposite a templating adenine over the cognate dT

SUBMITTER: Eckenroth BE 

PROVIDER: S-EPMC3843097 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature