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Elaborated Action of the Human Primosome #MMPMID28208743
Baranovskiy AG; Tahirov TH
Genes (Basel) 2017[Feb]; 8 (2): ä PMID28208743show 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 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.