4BPX

Crystal structure of human primase in complex with the primase- binding motif of DNA polymerase alpha

Summary for 4BPX

• Entry DOI: 10.2210/pdb4bpx/pdb
• Related: 4BPU 4BPW
• Descriptor: DNA PRIMASE SMALL SUBUNIT, DNA POLYMERASE ALPHA CATALYTIC SUBUNIT, DNA PRIMASE LARGE SUBUNIT, ZINC ION (3 entities in total)
• Functional Keywords: transferase, dna replication, fusion protein, chimera
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 4
• Total formula weight: 161894.97

Authors

Kilkenny, M.L.,Perera, R.L.,Pellegrini, L. (deposition date: 2013-05-28, release date: 2013-09-25, Last modification date: 2023-12-20)

Primary citation

Kilkenny, M.L.,Longo, M.,Perera, R.L.,Pellegrini, L.
Structures of Human Primase Reveal Design of Nucleotide Elongation Site and Mode of Pol Alpha Tethering
Proc.Natl.Acad.Sci.USA, 110:15961-, 2013

PubMed Abstract: Initiation of DNA synthesis in genomic duplication depends on primase, the DNA-dependent RNA polymerase that synthesizes de novo the oligonucleotides that prime DNA replication. Due to the discontinuous nature of DNA replication, primase activity on the lagging strand is required throughout the replication process. In eukaryotic cells, the presence of primase at the replication fork is secured by its physical association with DNA polymerase α (Pol α), which extends the RNA primer with deoxynucleotides. Our knowledge of the mechanism that primes DNA synthesis is very limited, as structural information for the eukaryotic enzyme has proved difficult to obtain. Here, we describe the crystal structure of human primase in heterodimeric form consisting of full-length catalytic subunit and a C-terminally truncated large subunit. We exploit the crystallographic model to define the architecture of its nucleotide elongation site and to show that the small subunit integrates primer initiation and elongation within the same set of functional residues. Furthermore, we define in atomic detail the mode of association of primase to Pol α, the critical interaction that keeps primase tethered to the eukaryotic replisome.

PubMed: 24043831
DOI: 10.1073/PNAS.1311185110

Experimental method

X-RAY DIFFRACTION (3.4 Å)