Lethal Mutations Within the Conserved Stem-loop of African Cassava Mosaic Virus DNA are Rapidly Corrected by Genomic Recombination

Roberts, S.E.; Stanley, John

doi:10.1099/0022-1317-75-11-3203

Cited by 47 publications

(32 citation statements)

References 43 publications

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“…Depending on where the mutation is introduced into the palindrome, either arm of the palindrome can be maintained to form a new palindrome or restored to the wild-type inverted repeats. Previous work with parvovirus (2) and geminivirus (28,34) has also demonstrated that mutilated inverted repeats engineered at the Ori can be accommodated or rapidly corrected.…”

Section: Discussionmentioning

confidence: 99%

“…As stated above, formation of a very stable and rigid cruciform structure at the onset of DNA replication will preclude correction of any mu-tilated sequence engineered into the left arm of the palindrome back to wild-type sequence or adoption of a mutilated right-arm sequence to form a new palindrome. In past studies, DNA replication and terminal repeat correction of the genomes of geminivirus (34), circular adenovirus (9), and circular adeno-associated virus (26) have been attributed to the RCR stem-loop cruciform model coupled with mechanisms of recombination, translocation, and panhandle gene correction (35), respectively. Potentially, the RCR melting-pot model described here for PCV1 is also applicable to other biological agents with circular genomes or circularized linear genomes.…”

Section: Discussionmentioning

confidence: 99%

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Detection of Template Strand Switching during Initiation and Termination of DNA Replication of Porcine Circovirus

Cheung

2004

J Virol

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Nucleotide substitution mutagenesis was conducted to investigate the importance of the inverted repeats (palindrome) at the origin of DNA replication (Ori) of porcine circovirus type 1 (PCV1). Viral genomes with engineered mutations on either arm or both arms of the palindrome were not impaired in protein synthesis and yielded infectious progeny viruses with restored or new palindromes. Thus, a flanking palindrome at the Ori was not essential for initiation of DNA replication, but one was generated inevitably at termination. Among the 26 viruses recovered, 16 showed evidence of template strand switching, from minus-strand genome DNA to palindromic strand DNA, during biosynthesis of the Ori. Here I propose a novel rolling-circle "melting-pot" model for PCV1 DNA replication. In this model, the replicator Rep protein complex binds, destabilizes, and nicks the Ori sequence to initiate leading-strand DNA synthesis. All four strands of the destabilized inverted repeats exist in a "melted" configuration, and the minus-strand viral genome and a palindromic strand are available as templates, simultaneously, during initiation or termination of DNA replication. Inherent in this model is a "gene correction" or "terminal repeat correction" mechanism that can restore mutilated invertedrepeat sequences to a palindrome at the Ori of circular DNAs or at the termini of circularized linear DNAs. Potentially, the melted state of the inverted repeats increases the rate of noncomplementary or illegitimate nucleotide incorporation into the palindrome. Thus, this melting-pot model provides insight into the mechanisms of DNA replication, gene correction, and illegitimate recombination at the Ori of PCV1, and it may be applicable to the replication of other circular DNA molecules.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Detection of Template Strand Switching during Initiation and Termination of DNA Replication of Porcine Circovirus

Cheung

2004

J Virol

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“…Within it, the invariant 9-nt sequence (TAATATT¡AC) contains the site (¡) where the initiation of ( +)strand DNA replication has been mapped in vivo [23,80,110,111] and in vitro [78,79]. The invariant loop sequence has a crucial role for viral DNA replication [38,112,113]. The structure of the stem is also important since point mutations which destroy base pairing are deleterious for viral replication, whereas those contributing to the maintenance of the stem-loop structure restore replication ability [114].…”

Section: Anatomy Of the ( +)Strand Dna Replication Originmentioning

confidence: 99%

Geminivirus DNA replication

Gutiérrez¹

1999

Cellular and Molecular Life Sciences (CMLS)

252

160

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Geminiviruses are DNA viruses which infect plants. They have a small genome and encode only a few proteins. Therefore, their DNA replication cycle relies largely on the use of cellular DNA replication proteins. The strategy used by geminiviruses to replicate their single-stranded DNA (ssDNA) genome consists of a first stage of conversion of ssDNA into double-stranded DNA (dsDNA) intermediates and, then, the use of dsDNA as a template to amplify viral dsDNA and to produce mature ssDNA genomes by a rolling-circle replication mechanism. In addition, the accumulating evidence indicates that viral DNA replication is somehow coupled to the cell cycle regulatory network of the infected cell. For these reasons, geminiviruses are excellent model systems to understand the regulation of DNA replication and cell cycle in plant cells. Recent years have witnessed significant progress in the identification of cis-acting signals and their interaction with trans-acting factors that contribute to geminivirus origin function. These and other aspects of the geminivirus DNA replication cycle will be reviewed.

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“…The common region seems to be a prime target for recombination. Homologous recombination between the common regions of ACMV DNA A and B was suggested as a repair mechanism to correct lethal substitutions and deletions in the DNA B stem-loop (Roberts & Stanley, 1994). Furthermore, constructs pCRA1 and pCRA2 contain extensive homologous sequences on both sides of the deletion in ∆11 while pJC1 contains homologous sequences only at the 3h end of the deletion (Fig.…”

Section: Discussionmentioning

confidence: 99%

Recombination between viral DNA and the transgenic coat protein gene of African cassava mosaic geminivirus.

Frischmuth¹,

Stanley²

1998

Journal of General Virology

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Nicotiana benthamiana was transformed with three different constructs (pCRA1, pCRA2 and pJC1) containing the coat protein coding sequence of African cassava mosaic virus (ACMV). Transformed plants were inoculated with a coat protein deletion mutant of ACMV that induces mild systemic symptoms in control plants. Several inoculated plants of transgenic lines CRA1/3, CRA1/4, CRA2/1 and CRA2/2 developed severe systemic symptoms typical of ACMV. DNA analysis revealed that, in these plants,

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Lethal Mutations Within the Conserved Stem-loop of African Cassava Mosaic Virus DNA are Rapidly Corrected by Genomic Recombination

Cited by 47 publications

References 43 publications

Detection of Template Strand Switching during Initiation and Termination of DNA Replication of Porcine Circovirus

Detection of Template Strand Switching during Initiation and Termination of DNA Replication of Porcine Circovirus

Geminivirus DNA replication

Recombination between viral DNA and the transgenic coat protein gene of African cassava mosaic geminivirus.

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