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The adenine misincorporated by replicative DNA polymerases (pols) opposite 7,8-dihydro-8-oxoguanine (8-oxo-G) is removed by a specific glycosylase, leaving the lesion on the DNA. Subsequent incorporation of C opposite 8-oxo-G on the resulting 1-nt gapped DNA is essential for the removal of the 8-oxo-G to prevent G-C to 1-A transversion mutations. By using model DNA templates, purified DNA pots β and λ and knockout cell extracts, we show here that the auxiliary proteins replication protein A and proliferating cell nuclear antigen act as molecular switches to activate the DNA pol λ- dependent highly efficient and faithful repair of A:8-oxo-G mismatches in human cells and to repress DNA pol β activity. By using an immortalized human fibroblast cell line that has the potential to induce cancer in mice, we show that the development of a tumoral phenotype in these cells correlated with a differential expression of DNA pols λ and β. [ABSTRACT FROM AUTHOR]

Discusses the modulation of the strand displacement activity of DNA polymerase gamma by the concerted action of replication protein A, proliferating cell nuclear antigen and flap endonuclease. Major polymerase involved in chromosomal replication in eukaryotes; Model for Okazaki fragment processing; Displacement by polymerase gamma of a newly synthesized strand on a minicircle template.