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

Item Type:Article
Title:Requirement of mammalian DNA polymerase-beta in base-excision repair
Creators Name:Sobol, R.W. and Horton, J.K. and Kühn, R. and Gu, H. and Singhal, R.K. and Prasad, R. and Rajewsky, K. and Wilson, S.H.
Abstract: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.
Keywords:Cell Division, Cell Line, Cell Survival, DNA Polymerase I, DNA Repair, Gene Deletion, Genetic Complementation Test, Germ-Line Mutation, Phenotype, Restriction Mapping, Transformed Cell Line, Animals, Mice
Source:Nature
ISSN:0028-0836
Publisher:Nature Publishing Group (U.K.)
Volume:379
Number:6561
Page Range:183-186
Date:11 January 1996
Official Publication:https://doi.org/10.1038/379183a0
PubMed:View item in PubMed

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