Mutational clusters generated by non-processive polymerases: A case study using DNA polymerase betain vitro.

DNA Repair
Libertad García-Villada, John W Drake

Abstract

Available DNA mutational spectra reveal that the number of mutants with multiple mutations ("multiples") is usually greater than expected from a random distribution of mutations among mutants. These overloads imply the occurrence of non-random clusters of mutations, probably generated during episodes of low-fidelity DNA synthesis. Excess multiples have been reported not only for viruses, bacteria, and eukaryotic cells but also for the DNA polymerases of phages T4 and RB69 in vitro. In the simplest case of a purified polymerase, non-random clusters may be generated by a subfraction of phenotypic variants able to introduce more errors per cycle of DNA synthesis than the normal enzyme. According to this hypothesis, excess multiples are not expected with non-processive polymerases even if they harbor rare mutator variants. DNA polymerase beta (Pol beta) is a mammalian DNA-repair polymerase with very low processivity. Although several Pol beta mutational spectra have been described, there is conflicting evidence on whether or not excess multiples occur, with spectra based on the HSV-tk system tending to show excess multiples. Excess multiples generated by Pol beta or any of its mutants might imply that the excesses of multiples obse...Continue Reading

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Citations

Apr 12, 2012·Proceedings of the National Academy of Sciences of the United States of America·Alireza G SenejaniJoann B Sweasy
May 25, 2010·Clinical & Experimental Ophthalmology·John Zhang, Mark D Stringer

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