Terminal deoxynucleotidyl transferase help DNA polymerase alpha bypass thymine dimer.

Abstract

The physiological function of terminal deoxynucleotidyl transferase (EC 2.7.7.31) is not known. In 1974, Baltimore (1) proposed a model in which terminal transferase acts as a somatic mutator at a special region of immunoglobulin gene during the maturation of immunocompetent cells. On the other hand, a speculative mechanism for induced mutagenesis in the eukaryotic cell was also discussed in connection with the possible induction of terminal transferase in the cell which has damaged DNA (2), In order to verify these hypothesis, further biochemical analysis may be required with respect to a possible modulation of the DNA polymerase reaction by terminal transferase. Recently, we have shown (3) that the replication by DNA polymerase α stops at the site of thymine dimer induced by ultraviolet-irradiation on the template poly(dT). The addition of terminal deoxynucleotidyl transferase to this system enhanced the DNA synthesis to the control level and it concemittantly increased the incorporation of the mismatched deoxynucleotides into the newly synthesized poly(dA) strand. The sizes of newly synthesized DNA were smaller with ultraviolet irradiated template but they increased to the control level with the addition of terminal deoxynucleotidyl transferase to the system. These results suggest that terminal deoxynucleotidyl transferase can help DNA polymerase α “bypass” thymine dimers in vitro by the formation of mismatched regions at the positions opposite to pyrimidine dimers on the template.