Replication protein A and proliferating cell nudear antigen coordinate DNA polymerase selection in 8-oxo-guanine repair.

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]