Changes in fidelity levels of DNA polymerases alpha-1, alpha-2, and beta during ageing in rats

DNA polymerases (deoxynucleoside-triphosphate:DNA deoxynucleotidyltransferase EC 2.7.7.7.) were extracted from the regenerating livers of rats of various ages. The extracts were separated into three DNA polymerase fractions (alpha-1, alpha-2, and beta) by phosphocellulose column chromatography, and their fidelity levels were then monitored with the synthetic template-primer, poly (dA-dT), poly dA-dT10, or poly dC-poly dG. The fidelity levels of the three DNA polymerases from regenerating liver of rats younger than 20 months were high, while those of DNA polymerases from rats older than 20 months were significantly lower with similar profiles on all three template-primers. On the other hand, the fidelity levels of enzymes from 23- and 26-month-old rats were similar. These results indicate that the levels of error-prone DNA polymerases increase rapidly in the regenerating liver of rats from ages 20 to 23 months. This may due to the amplification of DNA polymerase gene mutations by an error-prone enzyme itself. However, the cells in which mutations in the functional gene occur may undergo cell death because the fidelity levels of the DNA polymerases in the older animals did not increase.