Abstract
Abstract : Human DNA polymerases beta, eta, and kappa are enzymes that function in repairing damaged DNA. We set out to identify and characterize the role of prostate tumor mutations in human genes POLB, POLH and POLK. We discovered missense mutations in all three polymerase genes. Biochemical analysis of the polymerase beta missense variations showed that all of these somatic mutations affect either polymerase activity, enzyme stability, DNA synthesis fidelity, or a novel endonuclease activity. We further showed that the Pol beta endonuclease activity prevents aneuploidy and genomic instability. Thus, frequent polymerase mutations may contribute to prostate cancer progression, through distinct enzymatic functions. These mutations are valuable as biomarkers of cancer progression.
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