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Crystal structure of C-terminal domain of the human DNA primase large subunit with bound DNA template/RNA primer and manganese ionCrystal structure of C-terminal domain of the human DNA primase large subunit with bound DNA template/RNA primer and manganese ion
Structural highlights
FunctionPRI2_HUMAN DNA primase is the polymerase that synthesizes small RNA primers for the Okazaki fragments made during discontinuous DNA replication. Publication Abstract from PubMedThe human primosome, a 340 kilodalton complex of primase and DNA polymerase alpha (Pol alpha), synthesizes chimeric RNA-DNA primers to be extended by replicative DNA polymerases delta and . The intricate mechanism of concerted primer synthesis by two catalytic centers was an enigma for over three decades. Here we report the crystal structures of two key complexes, the human primosome and the C-terminal domain of the primase large subunit (p58C) with bound DNA/RNA duplex. These structures, along with analysis of primase/polymerase activities, provide a plausible mechanism for all transactions of the primosome including initiation, elongation, accurate counting of RNA primer length, primer transfer to Pol alpha, and concerted autoregulation of alternate activation/inhibition of the catalytic centers. Our findings reveal a central role of p58C in the coordinated actions of two catalytic domains in the primosome and ultimately could impact the design of anticancer drugs. MECHANISM OF CONCERTED RNA-DNA PRIMER SYNTHESIS BY THE HUMAN PRIMOSOME.,Baranovskiy AG, Babayeva ND, Zhang Y, Gu J, Suwa Y, Pavlov YI, Tahirov TH J Biol Chem. 2016 Mar 14. pii: jbc.M116.717405. PMID:26975377[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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