Evidence that errors made by DNA polymerase α are corrected by DNA polymerase δ

Y. I. Pavlov, C. Frahm, S. A.Nick McElhinny, A. Niimi, Motoshi Suzuki, T. A. Kunkel

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

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 ε. Pol δ and pol ε 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 ε. 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.

Original languageEnglish
Pages (from-to)202-207
Number of pages6
JournalCurrent Biology
Volume16
Issue number2
DOIs
Publication statusPublished - 24-01-2006
Externally publishedYes

Fingerprint

spleen exonuclease
DNA-directed DNA polymerase
DNA-Directed DNA Polymerase
DNA
Phenotype
phenotype
Genomic Instability
Eukaryota
Yeast
eukaryotic cells
Elongation
inactivation
Substitution reactions
Nucleotides
Genes
Yeasts
nucleotides
Alleles
Switches
RNA

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Pavlov, Y. I., Frahm, C., McElhinny, S. A. N., Niimi, A., Suzuki, M., & Kunkel, T. A. (2006). Evidence that errors made by DNA polymerase α are corrected by DNA polymerase δ. Current Biology, 16(2), 202-207. https://doi.org/10.1016/j.cub.2005.12.002
Pavlov, Y. I. ; Frahm, C. ; McElhinny, S. A.Nick ; Niimi, A. ; Suzuki, Motoshi ; Kunkel, T. A. / Evidence that errors made by DNA polymerase α are corrected by DNA polymerase δ. In: Current Biology. 2006 ; Vol. 16, No. 2. pp. 202-207.
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Pavlov, YI, Frahm, C, McElhinny, SAN, Niimi, A, Suzuki, M & Kunkel, TA 2006, 'Evidence that errors made by DNA polymerase α are corrected by DNA polymerase δ', Current Biology, vol. 16, no. 2, pp. 202-207. https://doi.org/10.1016/j.cub.2005.12.002

Evidence that errors made by DNA polymerase α are corrected by DNA polymerase δ. / Pavlov, Y. I.; Frahm, C.; McElhinny, S. A.Nick; Niimi, A.; Suzuki, Motoshi; Kunkel, T. A.

In: Current Biology, Vol. 16, No. 2, 24.01.2006, p. 202-207.

Research output: Contribution to journalArticle

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