DNA Polymerase δ-Dependent Formation of a Hairpin Structure at the 5′ Terminal Palindrome of the Minute Virus of Mice Genome

Cossons, Nandini; Faust, Emmanuel A.; Zannis‐Hadjopoulos, Maria

doi:10.1006/viro.1996.0058

Cited by 19 publications

(19 citation statements)

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“…However, p21 mutants that could bind cyclin͞cdk, but not PCNA, were shown to only achieve an incomplete inhibition of SV40 DNA replication in S cell extracts (9). In support of our conclusion, there is in vitro evidence for the participation of Pol ␦ in late parvovirus DNA replication steps, which, like conversion, involve a continuous unidirectional strand elongation process (16,34). Furthermore, we failed to inhibit the conversion reaction by adding anti-Pol ␣ neutralizing Abs in amounts that suppressed in vitro SV40 DNA replication (data not shown).…”

Section: Discussionsupporting

confidence: 73%

Cyclin A activates the DNA polymerase δ-dependent elongation machinery in vitro : A parvovirus DNA replication model

Bashir

Hörlein

Rommelaere

et al. 2000

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

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Replication of the single-stranded linear DNA genome of parvovirus minute virus of mice (MVM) starts with complementary strand synthesis from the 3 -terminal snap-back telomere, which serves as a primer for the formation of double-stranded replicative form (RF) DNA. This DNA elongation reaction, designated conversion, is exclusively dependent on cellular factors. In cell extracts, we found that complementary strand synthesis was inhibited by the cyclindependent kinase inhibitor p21 WAF1/CIP1 and rescued by the addition of proliferating cell nuclear antigen, arguing for the involvement of DNA polymerase (Pol) ␦ in the conversion reaction. In vivo time course analyses using synchronized MVM-infected A9 cells allowed initial detection of MVM RF DNA at the G1͞S phase transition, coinciding with the onset of cyclin A expression and cyclin A-associated kinase activity. Under in vitro conditions, formation of RF DNA was efficiently supported by A9 S cell extracts, but only marginally by G 1 cell extracts. Addition of recombinant cyclin A stimulated DNA conversion in G 1 cell extracts, and correlated with a concomitant increase in cyclin A-associated kinase activity. Conversely, a specific antibody neutralizing cyclin A-dependent kinase activity, abolished the capacity of S cell extracts for DNA conversion. We found no evidence for the involvement of cyclin E in the regulation of the conversion reaction. We conclude that cyclin A is necessary for activation of complementary strand synthesis, which we propose as a model reaction to study the cell cycle regulation of the Pol ␦-dependent elongation machinery. E ukaryotic DNA replication is restricted to the S phase of the cell cycle. Cell cycle progression is regulated through the action of cyclin-dependent kinases (cdks) that are sequentially activated on association with different cyclins (1). In vertebrate cells, the transition from G 1 to S phase is controlled by the activities of cyclin E-and cyclin A-dependent kinases (2). There is accumulating evidence for the involvement of cyclin A and cyclin E in the regulation of cellular DNA replication. Cyclin A is localized at nuclear replication foci in mammalian cells (3, 4), and both cyclin A and cdk2 have been found to be associated with replicating DNA in the simian virus 40 (SV40) in vitro replication system (5). Addition of recombinant cyclin A͞cdk2 and cyclin E͞cdk2 to G 1 phase nuclei has been shown to trigger the initiation of DNA replication in a human cell-free system (6). Similarly, the inability of human G 1 cell extracts to replicate SV40 origin-containing DNA in vitro could be overcome by the addition of cyclin A or active cdc2 kinase (7,8). Conversely, immunodepletion of cyclin A from S cell extracts partially inhibited SV40 origin-driven plasmid replication (9), whereas a significant decrease in the ability of Xenopus egg extracts to replicate sperm DNA was observed after depletion of cyclin E or cdk2 (10, 11). However, it has been difficult to identify replication factors that are targets for cdks in vivo a...

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Section: Discussionsupporting

confidence: 73%

Cyclin A activates the DNA polymerase δ-dependent elongation machinery in vitro : A parvovirus DNA replication model

Bashir

Hörlein

Rommelaere

et al. 2000

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

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“…These and other lines of evidence point to DNA polymerase ␦ as the enzyme responsible for parvovirus DNA replication (6). Here, we show that DNA polymerase ␦ indeed accumulates in APAR bodies in MVM-infected NBE cells (Fig.…”

supporting

confidence: 48%

In Vivo Accumulation of Cyclin A and Cellular Replication Factors in Autonomous Parvovirus Minute Virus of Mice-Associated Replication Bodies

Bashir

Rommelaere

Cziepluch

2001

J Virol

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Autonomous parvovirus minute virus of mice (MVM) DNA replication is strictly dependent on cellular factors expressed during the S phase of the cell cycle. Here we report that MVM DNA replication proceeds in specific nuclear structures termed autonomous parvovirus-associated replication bodies, where components of the basic cellular replication machinery accumulate. The presence of DNA polymerases ␣ and ␦ in these bodies suggests that MVM utilizes partially preformed cellular replication complexes for its replication. The recruitment of cyclin A points to a role for this cell cycle factor in MVM DNA replication beyond its involvement in activating the conversion of virion single-stranded DNA to the duplex replicative form.Autonomous parvoviruses and other members of the Parvoviridae family are unique among animal viruses in having linear single-stranded DNA genomes. The termini of their approximately 5,000-nucleotide genomes contain palindromic sequences which fold into stable hairpin structures and serve as primers for viral DNA synthesis. The replicative cycle, which takes place in the nucleus, is initiated by the synthesis of the cDNA strand leading to the formation of double-stranded replicative-form DNA. This reaction, also known as conversion, is exclusively dependent on cellular factors. In addition, the subsequent amplification reactions require the activity of the virus-encoded major nonstructural protein NS1 (7).Several cellular factors which are essential for DNA replication of the prototype autonomous parvovirus minute virus of mice (MVM) have been identified through cell fractionation and complementation assays in vitro replication systems (5,8,20). However, very little is known about the subnuclear organization of MVM DNA replication in vivo. In contrast to viruses with double-stranded DNA genomes that replicate in close proximity to preformed nuclear structures known as promyelocytic leukemia (PML) bodies (for review see reference 18), autonomous parvovirus H-1 was shown to induce characteristic nuclear structures, termed H-1 parvovirus-associated replication (PAR) bodies, which are unrelated to PML bodies (9). Similar structures were also characterized in Aleutian mink disease virus-infected cells (21,22). In this study, we aimed to determine whether MVM also establishes PAR bodylike structures in the nuclei of infected cells and to analyze the subnuclear distribution of cellular factors assumed to be involved in MVM DNA replication in vivo. To this end, A9 mouse cells were infected with MVMp at a multiplicity of infection of 10 PFU per cell. At 15 h postinfection, cells were labeled for 20 min with bromodeoxyuridine (BrdU) at a concentration of 10 M and then immediately fixed in 1% formaldehyde for 10 min at room temperature. BrdU incorporation into replicated viral DNA was detected with a BrdU-specific antibody (Becton Dickinson) without prior denaturation, thus excluding the detection of chromosomal DNA replication (21). Simultaneously, NS1 was detected with the NS1-specific SP8 antibody (11). ...

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“…The linear parvovirus genome has palindromic terminal sequences that can fold into hairpin duplexes (often Y-or T-shaped structure) that serve as primers for replication by host cell DNA polymerase @ (Cossons et al, 1996) and contain most of the cis-acting elements, both for replication and transcription . These telomers can vary in size from about 100 to over 500 nucleotides for the different parvoviruses.…”

Section: Parvovirus Infection and Replicationmentioning

confidence: 99%

Molecular and Structural Basis of the Evolution of Parvovirus Tropism

Tijssen¹

1999

Acta Veterinaria Hungarica

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DNA Polymerase δ-Dependent Formation of a Hairpin Structure at the 5′ Terminal Palindrome of the Minute Virus of Mice Genome

Cited by 19 publications

References 0 publications

Cyclin A activates the DNA polymerase δ-dependent elongation machinery in vitro : A parvovirus DNA replication model

Cyclin A activates the DNA polymerase δ-dependent elongation machinery in vitro : A parvovirus DNA replication model

In Vivo Accumulation of Cyclin A and Cellular Replication Factors in Autonomous Parvovirus Minute Virus of Mice-Associated Replication Bodies

Molecular and Structural Basis of the Evolution of Parvovirus Tropism

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