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Elaborated Action of the Human Primosome
#MMPMID28208743
Baranovskiy AG
; Tahirov TH
Genes (Basel)
2017[Feb]; 8
(2
): ? PMID28208743
show ga
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.
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