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Elaborated Action of the Human Primosome.


ABSTRACT: The human primosome is a 340-kilodalton complex of primase (DNA-dependent RNA polymerase) and DNA polymerase ?, which initiates genome replication by synthesizing chimeric RNA-DNA primers for DNA polymerases ? and ?. 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 Pol?, which works equally well on DNA:RNA and DNA:DNA double helices, intramolecularly catches the template primed by a 9mer 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.

SUBMITTER: Baranovskiy AG 

PROVIDER: S-EPMC5333051 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Elaborated Action of the Human Primosome.

Baranovskiy Andrey G AG   Tahirov Tahir H TH  

Genes 20170208 2


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  ...[more]

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