DNA polymerases and human disease

Nat Rev Genet. 2008 Aug;9(8):594-604. doi: 10.1038/nrg2345.


The human genome encodes at least 14 DNA-dependent DNA polymerases--a surprisingly large number. These include the more abundant, high-fidelity enzymes that replicate the bulk of genomic DNA, together with eight or more specialized DNA polymerases that have been discovered in the past decade. Although the roles of the newly recognized polymerases are still being defined, one of their crucial functions is to allow synthesis past DNA damage that blocks replication-fork progression. We explore the reasons that might justify the need for so many DNA polymerases, describe their function and mode of regulation, and finally consider links between mutations in DNA polymerases and human disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Chromosomes, Human / metabolism
  • Chromosomes, Human / physiology
  • DNA Replication / genetics
  • DNA Replication / physiology
  • DNA-Directed DNA Polymerase / genetics
  • DNA-Directed DNA Polymerase / metabolism
  • DNA-Directed DNA Polymerase / physiology*
  • Disease / etiology*
  • Drug Delivery Systems
  • Gene Expression Regulation, Enzymologic
  • Genome, Human / physiology
  • Humans
  • Models, Biological
  • Therapeutics


  • DNA-Directed DNA Polymerase