Open AccessReplication protein A and proliferating cell nuclear antigen coordinate DNA polymerase selection in 8-oxo-guanine repair
Author(s) -
Giovanni Maga,
Emmanuele Crespan,
Ursula Wimmer,
Barbara van Loon,
Alessandra Amoroso,
Chiara Mondello,
Cristina Belgiovine,
Elena Ferrari,
Giada A. Locatelli,
Giuseppe Villani,
Ulrich Hübscher
Publication year - 2008
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0811241106
Subject(s) - dna polymerase delta , proliferating cell nuclear antigen , biology , microbiology and biotechnology , dna replication , dna polymerase , dna polymerase ii , dna repair , dna clamp , dna , dna glycosylase , replication protein a , dna binding protein , genetics , gene , polymerase chain reaction , reverse transcriptase , transcription factor
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 T–A transversion mutations. By using model DNA templates, purified DNA pols 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.