A precursor terminal protein-trinucleotide intermediate during initiation of adenovirus DNA replication: regeneration of molecular ends in vitro by a jumping back mechanism.

King, Audrey J.; Vliet, Peter C. van der

doi:10.1002/j.1460-2075.1994.tb06917.x

Cited by 77 publications

(79 citation statements)

References 42 publications

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“…In addition, A-6 and to a small extent also A-7 modulate the VPg-uridylylation step and affect the yield of product. These results are consistent with a slide-back mechanism for the synthesis VPgpUpU, which is similar to the mechanism used by viral DNA polymerases such as that of adenovirus (26) and phages ⌽29 (27), PRD1 (28), GA-1 (29), and Cp-1 (30) that catalyze protein-primed DNA synthesis.…”

Section: Aaasupporting

confidence: 82%

A “Slide-back” Mechanism for the Initiation of Protein-primed RNA Synthesis by the RNA Polymerase of Poliovirus

Paul

Jiang

Mugavero

et al. 2003

Journal of Biological Chemistry

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Section: Aaasupporting

confidence: 82%

A “Slide-back” Mechanism for the Initiation of Protein-primed RNA Synthesis by the RNA Polymerase of Poliovirus

Paul

Jiang

Mugavero

et al. 2003

Journal of Biological Chemistry

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“…At position 4 from the 3Ј-end of the template a pTP⅐CAT intermediate is synthesized which jumps back to be paired to the template residues 1-3 before elongation starts (2). This jumping or sliding-back mechanism was first described for 29 (3) and appears to be universal for protein-priming replication systems (4 -6), enabling errors made during initiation and small deletions to be restored.…”

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confidence: 99%

Dissociation of the Protein Primer and DNA Polymerase after Initiation of Adenovirus DNA Replication

King

Teertstra

Vliet

1997

Journal of Biological Chemistry

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Initiation of adenovirus DNA replication occurs by a jumping back mechanism in which the precursor terminal priming protein (pTP) forms a pTP⅐trinucleotide complex (pTP⅐CAT) catalyzed by the viral DNA polymerase (pol). This covalent complex subsequently jumps back 3 bases to permit the start of chain elongation. Before initiation, pTP and pol form a tight heterodimer. We investigated the fate of this pTP⅐pol complex during the various steps in replication. Employing in vitro initiation and elongation on both natural viral templates and synthetic oligonucleotides followed by glycerol gradient separation of the reaction products, we established that pTP and pol are separated during elongation. Whereas pTP⅐C and pTP⅐CA were still bound to the polymerase, after the formation of pTP⅐CAT 60% of the pTP⅐pol complex had dissociated. Dissociation coincides with a change in sensitivity to inhibitors and in K m for dNTPs, suggesting a conformational change in the polymerase, both in the active site and in the pTP interaction domain. In agreement with this, the polymerase becomes a more efficient enzyme after release of the pTP primer. We also investigated whether the synthesis of a pTP initiation intermediate is confined to three nucleotides. Employing synthetic oligonucleotide templates with a sequence repeat of two nucleotides (GAGAGAGA . . . instead of the natural GTAGTA . . . ) we show that G5 rather than G3 is used to start, leading to a pTP⅐tetranucleotide (CTCT) intermediate that subsequently jumps back. This indicates flexibility in the use of the start site with a preference for the synthesis of three or four nucleotides during initiation rather than two.The replication of the linear 36-kilobase pair adenovirus (Ad) 1 DNA initiates at two origins located at either molecular end employing a protein-priming mechanism. Initiation requires at least two viral proteins, the DNA polymerase (pol) and the precursor of the terminal protein (pTP), which acts as the primer and is linked covalently to the first nucleotide, a dCMP molecule. Initiation can be stimulated by the cellular transcription factors NFI and Oct-1 which guide the pTP⅐pol complex to the core origin employing their DNA binding domains. This leads to stabilization of the preinitiation complex and increases the number of initiation events by enhancing the V max of the reaction. In addition, the virus-coded singlestranded DNA-binding protein stimulates initiation by lowering the K m for dCTP (1).The virus uses a jumping back mechanism for initiation. At position 4 from the 3Ј-end of the template a pTP⅐CAT intermediate is synthesized which jumps back to be paired to the template residues 1-3 before elongation starts (2). This jumping or sliding-back mechanism was first described for 29 (3) and appears to be universal for protein-priming replication systems (4 -6), enabling errors made during initiation and small deletions to be restored. Subsequent elongation concomitant with the displacement of the non-template strand further requires the Ad DNA-binding protei...

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“…The TP-dAMP initiation complex formed using as template the third 3Ј terminal nucleotide should not be directly elongated from the initiation site, because this would imply the lost of genetic information of the 2 first 3Ј nucleotides. Thus, in virtue of the terminal repetitions, various terminal sequence recovery mechanisms have evolved: ''slidingback,'' by which the initiation product translocates back 1 position, enabling the nucleotide used as template for the initiation reaction to direct also the insertion of the second nucleotide, as it has been described to occur in 29 (12) and in the 29-related bacteriophage GA-1 (14); ''stepwise sliding-back,'' that takes place in the S. pneumoniae phage Cp-1, which initiates at the 3Ј third nucleotide of its terminal repetition (3Ј-TTT) (15), and by the E. coli phage PRD1 that initiates at the 4th nucleotide (3Ј-CCCC) (16), requiring 2 and 3 consecutive sliding-back steps, respectively, to recover the DNA end information; ''jumping-back,'' described to occur in adenovirus, in which the initiation product TP-CAT, initially synthesized using as template the GTA sequence at positions 4-6 in the template, jumps back to the sequence GTA at positions 1 to 3 (17). These mechanisms have been envisaged to increase the fidelity during the initiation reaction, because several base pairing checking steps have to occur before definitive elongation of the initiation product takes place (12,13).…”

Section: Resultsmentioning

confidence: 99%

“…and Escherichia coli phage PRD1 (16) or variations of it, such as the jumping-back mechanism that takes place in adenovirus (17), seems to be a common theme of protein-priming replication systems to maintain full-length DNA (1,6). In addition, RNA viruses, such as Poliovirus, characterized by the presence of a protein covalently linked to the 5Ј end of the viral genome, have been also shown to initiate at internal positions with a further recovery of the terminal sequence by a sliding-back mechanism (18)(19)(20).…”

mentioning

confidence: 99%

Phage φ29 and Nf terminal protein-priming domain specifies the internal template nucleotide to initiate DNA replication

Longás¹,

Villar²,

Lázaro³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Bacteriophages 29 and Nf from Bacillus subtilis start replication of their linear genome at both DNA ends by a protein-primed mechanism, by which the DNA polymerase, in a template-instructed reaction, adds 5 -dAMP to a molecule of terminal protein (TP) to form the initiation product TP-dAMP. Mutational analysis of the 3 terminal thymines of the Nf DNA end indicated that initiation of Nf DNA replication is directed by the third thymine on the template, the recovery of the 2 terminal nucleotides mainly occurring by a stepwise sliding-back mechanism. By using chimerical TPs, constructed by swapping the priming domain of the related 29 and Nf proteins, we show that this domain is the main structural determinant that dictates the internal 3 nucleotide used as template during initiation.chimerical terminal protein ͉ polymerase ͉ linear genomes ͉ protein-primed replication ͉ sliding-back M any organisms, such as bacteriophages; animal viruses, such as adenovirus, mitochondrial plasmids, linear chromosomes and plasmids of Streptomyces (1); and more recently virus infecting Archaea, such as halovirus (2, 3), possess replication origins constituted by inverted terminal repetitions (ITR) with a terminal protein (TP) linked to both 5Ј ends of their linear chromosomes (4). In these cases, the location of the 2 replication origins allows both strands to be replicated continuously, without requiring asymmetric complexes of DNA polymerase with other accessory proteins to control the different mechanics of continuous and discontinuous DNA synthesis (5). Additionally, the TP provides the OH Ϫ group of a specific serine, threonine or tyrosine to prime initiation of DNA replication from the very ends of the linear chromosome, the TP remaining covalently linked to the 5Ј-DNA ends (parental TP) (1,4,6).The development of an in vitro replication system with highly purified proteins and DNA from bacteriophage 29 of B. subtilis has allowed to lay the foundations of the so-called proteinprimed mechanism of DNA replication (4, 6). 29 has a linear dsDNA, 19,285 bp long, containing a TP of 31 kDa covalently linked to each 5Ј end [TP-DNA (7)] that, together with a 6-bp inverted terminal repeat (3Ј-TTTCAT-5Ј) (8, 9) form part of a minimal replication origin. Once the replication origins are specifically recognized by a heterodimer formed by the DNA polymerase and a free TP molecule (10, 11), the DNA polymerase catalyzes the formation of a covalent bond between dAMP and the hydroxyl group of Ser 232 of the TP, a reaction directed by the second T at the 3Ј end (12). Then, the TP-dAMP initiation product translocates backwards 1 position to recover the template information corresponding to the first T, the so-called sliding-back mechanism, which requires a terminal repetition of 2 bp (12) and provides a way to prevent mutations at the 29 DNA ends during initiation, since the 3Ј-5Ј exonuclease activity of 29 DNA polymerase cannot proofread the TP-linked nucleotide (13).The sliding-back mechanism, occurring also in the 29-related phage GA-1 (14); S...

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A precursor terminal protein-trinucleotide intermediate during initiation of adenovirus DNA replication: regeneration of molecular ends in vitro by a jumping back mechanism.

Cited by 77 publications

References 42 publications

A “Slide-back” Mechanism for the Initiation of Protein-primed RNA Synthesis by the RNA Polymerase of Poliovirus

A “Slide-back” Mechanism for the Initiation of Protein-primed RNA Synthesis by the RNA Polymerase of Poliovirus

Dissociation of the Protein Primer and DNA Polymerase after Initiation of Adenovirus DNA Replication

Phage φ29 and Nf terminal protein-priming domain specifies the internal template nucleotide to initiate DNA replication

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