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

EMBO J. 2000 Apr 3;19(7):1731-42. doi: 10.1093/emboj/19.7.1731.


A novel DNA polymerase has been identified in human cells. Human DNA polymerase mu (Pol mu), consisting of 494 amino acids, has 41% identity to terminal deoxynucleotidyltransferase (TdT). Human Pol mu, 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 mu 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 mu mRNA in peripheral lymphoid tissues. Moreover, a large proportion of the human expressed sequence tags corresponding to Pol mu, present in the databases, derived from germinal center B cells. Therefore, Pol mu is a good candidate to be the mutator polymerase responsible for somatic hyper- mutation of immunoglobulin genes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Cell Line
  • Chromosome Mapping
  • Chromosomes, Human, Pair 7 / genetics
  • DNA / genetics*
  • DNA / metabolism*
  • DNA Nucleotidylexotransferase / genetics
  • DNA Nucleotidylexotransferase / metabolism*
  • DNA Primers / genetics
  • DNA-Directed DNA Polymerase / genetics
  • DNA-Directed DNA Polymerase / metabolism*
  • Escherichia coli / genetics
  • Gene Expression
  • Genes, Immunoglobulin
  • Humans
  • In Situ Hybridization
  • In Vitro Techniques
  • Lymphoid Tissue / enzymology
  • Molecular Sequence Data
  • Mutation*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid


  • DNA Primers
  • RNA, Messenger
  • Recombinant Proteins
  • DNA
  • DNA polymerase mu
  • DNA Nucleotidylexotransferase
  • DNA-Directed DNA Polymerase