Elaborated action of the human primosome

Andrey G. Baranovskiy, Tahir H Tahirov

Research output: Contribution to journalReview article

12 Scopus citations

Abstract

The human primosome is a 340-kilodalton complex of primase (DNA-dependent RNA polymerase) and DNA polymerase α, which initiates genome replication by synthesizing chimeric RNA-DNA primers for DNA polymerases δ and ε. Accumulated biochemical and structural data reveal the complex mechanism of concerted primer synthesis by two catalytic centers. First, primase generates an RNA primer through three steps: initiation, consisting of dinucleotide synthesis from two nucleotide triphosphates; elongation, resulting in dinucleotide extension; and termination, owing to primase inhibition by a mature 9-mer primer. Then Polα, which works equally well on DNA:RNA and DNA:DNA double helices, intramolecularly catches the template primed by a 9-mer RNA and extends the primer with dNTPs. All primosome transactions are highly coordinated by autoregulation through the alternating activation/inhibition of the catalytic centers. This coordination is mediated by the small C-terminal domain of the primase accessory subunit, which forms a tight complex with the template:primer, shuttles between the primase and DNA polymerase active sites, and determines their access to the substrate.

Original languageEnglish (US)
Article number62
JournalGenes
Volume8
Issue number2
DOIs
Publication statusPublished - Feb 8 2017

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Keywords

  • DNA polymerase α
  • DNA replication
  • Human
  • Initiation
  • Primase
  • Primosome
  • Protein-DNA interaction
  • RNA synthesis
  • Steric hindrance
  • Termination

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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