Abstract
SYNTHESIS of DNA by DNA polymerase-β is distributive on single-stranded DNA templates, but short DNA gaps with a 5′ PO4 in the gap are filled processively to completion1,2. In vitro studies have suggested a role of β-polymerase in different types of DNA repair3–9. However, the significance of these studies to the in vivo role of β-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-β. Extracts from these cell lines were found to be defective in uracil-initiated base-excision repair. The β-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 β-polymerase minitransgene. These studies demonstrate that β-polymerase functions specifically in base-excision repair in vivo.
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Sobol, R., Horton, J., Kühn, R. et al. Requirement of mammalian DNA polymerase-β in base-excision repair. Nature 379, 183–186 (1996). https://doi.org/10.1038/379183a0
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DOI: https://doi.org/10.1038/379183a0
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