Evidence that Errors Made by DNA Polymerase α are Corrected by DNA Polymerase δ

• Published in: Current biology 2006-01, Vol.16 (2), p.202-207
• Main Authors: Pavlov, Y.I., Frahm, C., McElhinny, S.A. Nick, Niimi, A., Suzuki, M., Kunkel, T.A.
• Format: Article
• Language: English
• Subjects: Catalysis; DNA; DNA Polymerase I - physiology; DNA Polymerase II - physiology; DNA Polymerase III - physiology; DNA Replication - physiology; DNA, Fungal - biosynthesis; DNA, Fungal - metabolism; Exonucleases - physiology; Genomic Instability; Mutagenesis; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae - genetics
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2005.12.002

Eukaryotic replication [1, 2] begins at origins and on the lagging strand with RNA-primed DNA synthesis of a few nucleotides by polymerase α, which lacks proofreading activity. A polymerase switch then allows chain elongation by proofreading-proficient pol δ and pol ɛ. Pol δ and pol ɛ are essential, but their roles in replication are not yet completely defined [3]. Here, we investigate their roles by using yeast pol α with a Leu868Met substitution [4]. L868M pol α copies DNA in vitro with normal activity and processivity but with reduced fidelity. In vivo, the pol1-L868M allele confers a mutator phenotype. This mutator phenotype is strongly increased upon inactivation of the 3′ exonuclease of pol δ but not that of pol ɛ. Several nonexclusive explanations are considered, including the hypothesis that the 3′ exonuclease of pol δ proofreads errors generated by pol α during initiation of Okazaki fragments. Given that eukaryotes encode specialized, proofreading-deficient polymerases with even lower fidelity than pol α [5], such intermolecular proofreading could be relevant to several DNA transactions that control genome stability.