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 language | English (US) |
|---|---|
| Pages (from-to) | 202-207 |
| Number of pages | 6 |
| Journal | Current Biology |
| Volume | 16 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jan 24 2006 |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)
Cite this
Evidence that errors made by DNA polymerase α are corrected by DNA polymerase δ. / Pavlov, Youri I; Frahm, C.; McElhinny, S. A Nick; Niimi, A.; Suzuki, M.; Kunkel, T. A.
In: Current Biology, Vol. 16, No. 2, 24.01.2006, p. 202-207.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Evidence that errors made by DNA polymerase α are corrected by DNA polymerase δ
AU - Pavlov, Youri I
AU - Frahm, C.
AU - McElhinny, S. A Nick
AU - Niimi, A.
AU - Suzuki, M.
AU - Kunkel, T. A.
PY - 2006/1/24
Y1 - 2006/1/24
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=30944452765&partnerID=8YFLogxK
U2 - 10.1016/j.cub.2005.12.002
DO - 10.1016/j.cub.2005.12.002
M3 - Article
C2 - 16431373
AN - SCOPUS:30944452765
VL - 16
SP - 202
EP - 207
JO - Current Biology
JF - Current Biology
SN - 0960-9822
IS - 2
ER -