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Publication Abstract from PubMed

The Polalpha/primase complex assembles the short RNA-DNA fragments for priming of lagging and leading strand DNA replication in eukaryotes. As such, the Polalpha polymerase subunit encounters two types of substrates during primer synthesis: an RNA:DNA helix and a DNA:DNA helix. The engagement of the polymerase subunit with the DNA:DNA helix has been suggested as the of basis for primer termination in eukaryotes. However, there is no structural information on how the Polalpha polymerase subunit actually engages with a DNA:DNA helix during primer synthesis. We present here the first crystal structure of human Polalpha polymerase subunit in complex with a DNA:DNA helix. Unexpectedly, we find that portion of the DNA:DNA helix in contact with the polymerase is not in a B-form but in a hybrid A-B form. Almost all of the contacts observed previously with an RNA primer are preserved with a DNA primer - with the same set of polymerase residues tracking the sugar-phosphate backbone of the DNA or RNA primer. Thus, rather than loss of specific contacts, the free energy cost of distorting DNA from B- to hybrid A-B form may augur the termination of primer synthesis in eukaryotes.

Human DNA polymerase alpha in binary complex with a DNA:DNA template-primer.,Coloma J, Johnson RE, Prakash L, Prakash S, Aggarwal AK Sci Rep. 2016 Apr 1;6:23784. doi: 10.1038/srep23784. PMID:27032819^[2]

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