4b08

Yeast DNA polymerase alpha, Selenomethionine proteinYeast DNA polymerase alpha, Selenomethionine protein

Structural highlights

4b08 is a 1 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.67Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DPOLA_YEAST Catalytic component of DNA polymerase alpha, which in complex with DNA primase (DNA polymerase alpha:primase) constitutes a replicative polymerase (PubMed:10898792, PubMed:22119860, PubMed:31488849). POL1 has a role in promoting telomere replication during interaction with CDC13 (PubMed:10898792).^[1] ^[2] ^[3]

Publication Abstract from PubMed

The DNA Polymerase alpha (Pol alpha)/primase complex initiates DNA synthesis in eukaryotic replication. In the complex, Pol alpha and primase cooperate in the production of RNA-DNA oligonucleotides that prime synthesis of new DNA. Here we report crystal structures of the catalytic core of yeast Pol alpha in unliganded form, bound to an RNA primer/DNA template and extending an RNA primer with deoxynucleotides. We combine the structural analysis with biochemical and computational data to demonstrate that Pol alpha specifically recognizes the A-form RNA/DNA helix and that the ensuing synthesis of B-form DNA terminates primer synthesis. The spontaneous release of the completed RNA-DNA primer by the Pol alpha/primase complex simplifies current models of primer transfer to leading- and lagging strand polymerases. The proposed mechanism of nucleotide polymerization by Pol alpha might contribute to genomic stability by limiting the amount of inaccurate DNA to be corrected at the start of each Okazaki fragment. DOI:http://dx.doi.org/10.7554/eLife.00482.001.

Mechanism for priming DNA synthesis by yeast DNA Polymerase alpha.,Perera RL, Torella R, Klinge S, Kilkenny ML, Maman JD, Pellegrini L Elife. 2013 Apr 2;2:e00482. doi: 10.7554/eLife.00482. Print 2013. PMID:23599895^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Qi H, Zakian VA. The Saccharomyces telomere-binding protein Cdc13p interacts with both the catalytic subunit of DNA polymerase alpha and the telomerase-associated est1 protein. Genes Dev. 2000 Jul 15;14(14):1777-88. PMID:10898792
↑ Netz DJ, Stith CM, Stumpfig M, Kopf G, Vogel D, Genau HM, Stodola JL, Lill R, Burgers PM, Pierik AJ. Eukaryotic DNA polymerases require an iron-sulfur cluster for the formation of active complexes. Nat Chem Biol. 2011 Nov 27;8(1):125-32. doi: 10.1038/nchembio.721. PMID:22119860 doi:http://dx.doi.org/10.1038/nchembio.721
↑ Zhou ZX, Lujan SA, Burkholder AB, Garbacz MA, Kunkel TA. Roles for DNA polymerase delta in initiating and terminating leading strand DNA replication. Nat Commun. 2019 Sep 5;10(1):3992. doi: 10.1038/s41467-019-11995-z. PMID:31488849 doi:http://dx.doi.org/10.1038/s41467-019-11995-z
↑ Perera RL, Torella R, Klinge S, Kilkenny ML, Maman JD, Pellegrini L. Mechanism for priming DNA synthesis by yeast DNA Polymerase alpha. Elife. 2013 Apr 2;2:e00482. doi: 10.7554/eLife.00482. Print 2013. PMID:23599895 doi:http://dx.doi.org/10.7554/eLife.00482

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OCA

[1] Qi H, Zakian VA. The Saccharomyces telomere-binding protein Cdc13p interacts with both the catalytic subunit of DNA polymerase alpha and the telomerase-associated est1 protein. Genes Dev. 2000 Jul 15;14(14):1777-88. PMID:10898792

[2] Netz DJ, Stith CM, Stumpfig M, Kopf G, Vogel D, Genau HM, Stodola JL, Lill R, Burgers PM, Pierik AJ. Eukaryotic DNA polymerases require an iron-sulfur cluster for the formation of active complexes. Nat Chem Biol. 2011 Nov 27;8(1):125-32. doi: 10.1038/nchembio.721. PMID:22119860 doi:http://dx.doi.org/10.1038/nchembio.721

[3] Zhou ZX, Lujan SA, Burkholder AB, Garbacz MA, Kunkel TA. Roles for DNA polymerase delta in initiating and terminating leading strand DNA replication. Nat Commun. 2019 Sep 5;10(1):3992. doi: 10.1038/s41467-019-11995-z. PMID:31488849 doi:http://dx.doi.org/10.1038/s41467-019-11995-z

[4] Perera RL, Torella R, Klinge S, Kilkenny ML, Maman JD, Pellegrini L. Mechanism for priming DNA synthesis by yeast DNA Polymerase alpha. Elife. 2013 Apr 2;2:e00482. doi: 10.7554/eLife.00482. Print 2013. PMID:23599895 doi:http://dx.doi.org/10.7554/eLife.00482

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