Abstract 3121: Systematic analysis of the DNA synthesis fidelity of somatic mutations of polymerase beta found in prostate cancer

Abstract

Abstract Human DNA polymerase beta (polβ) is a monomeric protein of 335 amino acids and functions in base excision repair and meiotic recombination. Human polα is over-expressed in many cancer cells like ovarian, prostate, breast, colon and chronic myelogenous leukemia. To obtain clues of possible functions in vivo, we have determined the fidelity of DNA synthesis of polα with forward mutation assay which scored the sequence errors caused in the lacZ-α gene in M13mp2 during DNA synthesis to fill a 407-nucleotide gap. Three of seven of the somatic polα mutants, p.E232K, p.E123K and pE216K, which we identified previously in prostate tumors, were tested. The results indicated that the somatic mutants of human DNA polymerase beta display altered fidelity. The fidelity for large deletions and complex changes of the pE232K and pE123K muatants are three and 31 times lower respectively, compared to wild type polα. The T>G transversion at position 103, which is the most common feature of polB base substitution error spectrum, is observed six times and two times lower for the pE123K and p.E216K mutants than wild polymerase beta. Our data show that somatic mutations in prostate cancer change both the synthesis fidelity and/or mutation type compared with wild type polymerase beta. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3121. doi:1538-7445.AM2012-3121