Download MendeleyMechanism for priming DNA synthesis by yeast DNA Polymerase alpha
Perera, R.L., Torella, R., Klinge, S., Kilkenny, M.L., Maman, J.D., Pellegrini, L.(2013) Elife 2: e00482
- PubMed: 23599895
- DOI: https://doi.org/10.7554/eLife.00482
- Primary Citation of Related Structures:
4B08, 4FVM, 4FXD, 4FYD - PubMed Abstract:
The DNA Polymerase α (Pol α)/primase complex initiates DNA synthesis in eukaryotic replication. In the complex, Pol α 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 α 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 α 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 α/primase complex simplifies current models of primer transfer to leading- and lagging strand polymerases. The proposed mechanism of nucleotide polymerization by Pol α 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.
Organizational Affiliation:
Department of Biochemistry , University of Cambridge , Cambridge , United Kingdom.
