Requirement of mammalian DNA polymerase-beta in base-excision repair

Nature. 1996 Jan 11;379(6561):183-6. doi: 10.1038/379183a0.


Synthesis of DNA by DNA polymerase-beta is distributive on single-stranded DNA templates, but short DNA gaps with a 5' PO4 in the gap are filled processively to completion. In vitro studies have suggested a role of beta-polymerase in different types of DNA repair. However, the significance of these studies to the in vivo role of beta-polymerase has remained unclear. Because genetic studies are essential for determining the physiological role of a gene, we established embryonic fibroblast cell lines homozygous for a deletion mutation in the gene encoding DNA polymerase-beta. Extracts from these cell lines were found to be defective in uracil-initiated base-excision repair. The beta-polymerase-deleted cells are normal in viability and growth characteristics, although they exhibit increased sensitivity to monofunctional DNA-alkylating agents, but not to other DNA-damaging agents. Both the deficiency in base-excision repair and hypersensitivity to DNA-alkylating agents are rescued following stable transfection with a wild-type beta-polymerase minitransgene. These studies demonstrate that beta-polymerase functions specifically in base-excision repair in vivo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Division
  • Cell Line
  • Cell Line, Transformed
  • Cell Survival
  • DNA Polymerase I / metabolism*
  • DNA Repair*
  • Gene Deletion
  • Genetic Complementation Test
  • Germ-Line Mutation
  • Mice
  • Mice, Transgenic
  • Phenotype
  • Restriction Mapping


  • DNA Polymerase I