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New understanding of DNA replication

last modified Apr 03, 2013 12:24 PM

Luca Pellegrini's group has just published a paper in the new open-access journal Elife. Using a combination of crystallographic, biochemical and computational evidence they have shed light on the initiation of DNA synthesis in eukaryotic replication. The DNA Polymerase α (Pol α)/primase complex initiates DNA synthesis. In the complex, Pol α and primase cooperate in the production of RNA-DNA oligonucleotides that prime synthesis of new DNA. The group solved crystal structures for the catalytic core of yeast Pol α  by itself, bound to an RNA primer/DNA template and extending an RNA primer with deoxynucleotides. Using additional biochemical and computational data they showed that Pol α recognizes the A-form RNA/DNA helix and then synthesis of B-form DNA terminates primer synthesis. The release of the completed RNA-DNA primer by the Pol α/primase complex suggests a simpler model of primer transfer. The proposed mechanism of nucleotide polymerization by Pol α might contribute to genomic stability by limiting the amount of inaccurate DNA to be corrected.