Genome Protection by DNA Polymerase θ

Annu Rev Genet. 2022 Nov 30:56:207-228. doi: 10.1146/annurev-genet-072920-041046. Epub 2022 Aug 26.


DNA polymerase θ (Pol θ) is a DNA repair enzyme widely conserved in animals and plants. Pol θ uses short DNA sequence homologies to initiate repair of double-strand breaks by theta-mediated end joining. The DNA polymerase domain of Pol θ is at the C terminus and is connected to an N-terminal DNA helicase-like domain by a central linker. Pol θ is crucial for maintenance of damaged genomes during development, protects DNA against extensive deletions, and limits loss of heterozygosity. The cost of using Pol θ for genome protection is that a few nucleotides are usually deleted or added at the repair site. Inactivation of Pol θ often enhances the sensitivity of cells to DNA strand-breaking chemicals and radiation. Since some homologous recombination-defective cancers depend on Pol θ for growth, inhibitors of Pol θ may be useful in treating such tumors.

Keywords: DNA double-strand breaks; DNA helicase; DNA polymerases; DNA repair; mutations; translesion DNA synthesis.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA
  • DNA Damage / genetics
  • DNA End-Joining Repair / genetics
  • DNA Polymerase theta
  • DNA-Directed DNA Polymerase* / genetics
  • DNA-Directed DNA Polymerase* / metabolism
  • Neoplasms* / genetics


  • DNA-Directed DNA Polymerase
  • DNA