5IUD

Human DNA polymerase alpha in binary complex with a DNA:DNA template-primer

Summary for 5IUD

• Entry DOI: 10.2210/pdb5iud/pdb
• Descriptor: DNA polymerase alpha catalytic subunit, DNA template, DNA primer, ... (4 entities in total)
• Functional Keywords: dna polymerase binary complex, transferase-dna complex, transferase/dna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 12
• Total formula weight: 456056.96

Authors

Coloma, J.,Aggarwal, A.K. (deposition date: 2016-03-17, release date: 2016-04-13, Last modification date: 2024-03-06)

Primary citation

Coloma, J.,Johnson, R.E.,Prakash, L.,Prakash, S.,Aggarwal, A.K.
Human DNA polymerase alpha in binary complex with a DNA:DNA template-primer.
Sci Rep, 6:23784-23784, 2016

PubMed Abstract: The Polα/primase complex assembles the short RNA-DNA fragments for priming of lagging and leading strand DNA replication in eukaryotes. As such, the Polα 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 Polα polymerase subunit actually engages with a DNA:DNA helix during primer synthesis. We present here the first crystal structure of human Polα 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.

PubMed: 27032819
DOI: 10.1038/srep23784

Experimental method

X-RAY DIFFRACTION (3.3 Å)