Beta-polymerase is one of the few mammalian DNA repair genes which have been isolated. This enzyme is responsible for the repair polymerase step (""""""""gap filling"""""""" step) of DNA repair. In the case of short patch repair after damage by base damaging agents such as alkylating agents, Beta-polymerase is the only polymerase utilized. The genes of repair polymerases in E. coli and yeast have been found to be DNA-damage inducible. In collaboration with S. Wilson who has cloned both human and rat Beta-polymerase cDNA, we have found that Beta-polymerase RNA is rapidly induced in Chinese hamster ovary (CHO) cells after exposure of the cells to alkylating agents or hydrogen peroxide. Induction did not occur after UV radiation, heat shock, perturbation of cell cycle, or exposure to other DNA damaging agents which did not induce high levels of adducts to single bases in DNA. This is the first demonstration of the induction of a DNA repair gene in higher eukaryotic cells specifically by DNA damage. In order to further elucidate the regulation of Beta-polymerase in CHO cells, we have isolated the Beta-polymerase cDNA clone from a CHO cDNA library. Sequence analysis demonstrated that Beta-polymerase has been highly conserved in the Chinese hamster, rat, and human species. In collaboration with S. Wilson, we have found evidence that a DNA-damage-inducible trans-acting protein binds to the Beta-polymerase promoter, and can lead to increased transcription of this gene. Recently, we have found evidence that the regulation of the Beta-polymerase may involve one or more cellular kinases.
