DNA polymerase mu (Pol μ), homologous to TdT, could act as a DNA mutator in eukaryotic cells

A novel DNA polymerase has been identified in human cells. Human DNA polymerase mu (Pol μ), consisting of 494 amino acids, has 41% identity to terminal deoxynucleotidyltransferase (TdT). Human Pol μ, overproduced in Escherichia coli in a soluble form and purified to homogeneity, displays intrinsic terminal deoxynucleotidyltransferase activity and a strong preference for activating Mn 2+ ions. Interestingly, unlike TdT, the catalytic efficiency of polymerization carried out by Pol μ was enhanced by the presence of a template strand. Using activating Mg 2+ ions, template‐enhanced polymerization was also template‐directed, leading to the preferred insertion of complementary nucleotides, although with low discrimination values. In the presence of Mn 2+ ions, template‐enhanced polymerization produced a random insertion of nucleotides. Northern‐blotting and in situ analysis showed a preferential expression of Pol μ mRNA in peripheral lymphoid tissues. Moreover, a large proportion of the human expressed sequence tags corresponding to Pol μ, present in the databases, derived from germinal center B cells. Therefore, Pol μ is a good candidate to be the mutator polymerase responsible for somatic hypermutation of immunoglobulin genes.