Induction of the DNA repair enzymes uracil DNA glycosylase and 3-methyladenine DNA glycosylase in regenerating rat liver

The capacity of eukaryotic cells to modulate the activitiesof DNA repair enzymes during cell proliferation was examined.Using regenerating rat liver as a model system, the specificactivities of the DNA repair enzymes uracil DNA glycosylaseand 3-methyladenine DNA glycosylase were determined at specificintervals after partial hepatectomy. The induction of DNA replicationand the stimulation of DNA polymerase were also measured inorder to relate changes in the potential for DNA repair to thoseobserved for DNA replication. As measured in nuclear extracts,the specific activities of both the uracil DNA glycosylase andthe 3-methyladenine DNA glycosylase were increased in regeneratingrat liver reaching maximal levels 18–24 h after partialhepatectomy. The specific activity of each DNA repair enzymereturned to basal levels by 48 h after the hepatectomy. No increasein either enzyme activity was observed in sham operated controls.The products of the reactions were identified as 3-methyladenineor as uracil by high pressure liquid chromatography or by gelfiltration on Sephadex G-10. The 2–3 fold increases inthe specific activity observed for each nuclear DNA repair enzymewas comparable to the 2.7 fold increase observed for DNA polymeraseactivity. The stimulation of DNA repair enzymes in regeneratingrat liver is a further suggestion that eukaryotic cells activelyregulate excision repair pathways in the defined pattern ofgene expression observed during the eukaryotic cell cycle.