4FXD: Crystal structure of yeast DNA polymerase alpha bound to DNA/RNA

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.
PDB ID: 4FXDDownload
MMDB ID: 107952
PDB Deposition Date: 2012/7/3
Updated in MMDB: 2018/06
Experimental Method:
x-ray diffraction
Resolution: 3  Å
Source Organism:
Saccharomyces cerevisiae S288C
Similar Structures:
Biological Unit for 4FXD: trimeric; determined by author and by software (PISA)
Molecular Components in 4FXD
Label Count Molecule
Protein (1 molecule)
DNA Polymerase Alpha Catalytic Subunit a(Gene symbol: POL1)
Molecule annotation
Nucleotides(2 molecules)
DNA (5'-d(*tp*tp*tp*tp*cp*gp*cp*tp*gp*cp*cp*cp*gp*cp*cp*t)-3')
Molecule annotation
RNA (5'-r(*ap*gp*gp*cp*gp*gp*gp*cp*ap*g)-3')
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB