4bpu
Crystal structure of human primase in heterodimeric form, comprising PriS and truncated PriL lacking the C-terminal Fe-S domain.Crystal structure of human primase in heterodimeric form, comprising PriS and truncated PriL lacking the C-terminal Fe-S domain.
Structural highlights
FunctionPRI1_HUMAN DNA primase is the polymerase that synthesizes small RNA primers for the Okazaki fragments made during discontinuous DNA replication. Publication Abstract from PubMedInitiation 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 alpha (Pol alpha), 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 alpha, the critical interaction that keeps primase tethered to the eukaryotic replisome. Structures of human primase reveal design of nucleotide elongation site and mode of Pol alpha tethering.,Kilkenny ML, Longo MA, Perera RL, Pellegrini L Proc Natl Acad Sci U S A. 2013 Sep 16. PMID:24043831[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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