RNA facilitates RecA-mediated DNA pairing and strand transfer between molecules bearing limited regions of homology

Kotani, Hidehito; Germann, Markus W.; Andrus, Alex; Vinayak, Ravi; Mullah, Bashar; Kmiec, Eric B.

doi:10.1007/s004380050115

Cited by 18 publications

(14 citation statements)

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“…The first model suggests that DPS1 and DPS2 regulate transcription of one or more RNAs that act in cis, spreading outward along the chromosome from their site of synthesis to enhance the recombinational potential of DNA with which they are associated. How such an RNA or RNAs would promote recombination is not known, although RNA as a recombination enhancer is not unprecedented (Kotani et al 1996;Yoon et al 1996). Several precedents exist for cis-acting RNAs that profoundly affect the behavior of the associated chromosome.…”

Section: Models For the Role Of ␣2p In Donor Preferencementioning

confidence: 99%

α2p controls donor preference during mating type interconversion in yeast by inactivating a recombinational enhancer of chromosome III

Szeto¹,

Fafalios²,

Zhong³

et al. 1997

Genes Dev.

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Homothallic strains of Saccharomyces cerevisiae can change mating type as often as every generation by replacing the allele at the MAT locus with a copy of mating type information present at one of two storage loci, HML and HMR, located on either end of chromosome III. Selection of the appropriate donor locus is dictated by a mating type-specific repressor protein, ␣2p: Cells containing ␣2p select HMR, whereas those lacking ␣2p select HML.

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Section: Models For the Role Of ␣2p In Donor Preferencementioning

confidence: 99%

α2p controls donor preference during mating type interconversion in yeast by inactivating a recombinational enhancer of chromosome III

Szeto¹,

Fafalios²,

Zhong³

et al. 1997

Genes Dev.

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show abstract

“…RNA, a product of transcription, plays a role in extending the half-life of DNA molecules during the initial phase of recombination. They observed that the length of the complementary sequence required for stable DNA pairing might be reduced when one of the molecules contains RNA [21]. As DNA pairing is the rate-limiting step during homologous recombination, they tried to control this phase to improve the frequency of gene targeting.…”

Section: The Basis Of a Newly Developed Strategymentioning

confidence: 98%

Prospects of chimeric RNA-DNA oligonucleotides in gene therapy

Liu

Liang

2001

J Biomed Sci

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A strategy called targeted gene repair was developed to facilitate the process of gene therapy using a chimeric RNA-DNA oligonucleotide. Experiments demonstrated the feasibility of using the chimeric oligonucleotide to introduce point conversion in genes in vitro and in vivo. However, barriers exist in the low and/or inconstant frequency of gene repair. To overcome this difficulty, three main aspects should be considered. One is designing a more effective structure of the oligonucleotide. Trials have included lengthening the homologous region, displacing the mismatch on the chimeric strand and inventing a novel thioate-modified single-stranded DNA, which was demonstrated to be more active than the primary chimera in cell-free extracts. The second aspect is optimizing the delivery system. Producing synthetic carriers for efficient and specific transfection is demanding, especially for treatment in vivo where targeting is difficult. The third and most important aspect lies in the elucidation of the mechanism of the strategy. Investigation of the mechanism of strand exchange between the oligonucleotide molecule and double-stranded DNA in prokaryotes may greatly help to understand the mechanism of gene repair in eukaryotes. The development of this strategy holds great potential for the treatment of genetic defects and other purposes.

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“…131,132 The initial chimeraplast design was a contiguous stretch of 68 nucleotides containing both RNA and DNA residues (Fig. 5A).…”

Section: Gene Repair Strategiesmentioning

confidence: 99%

Gene therapy as an alternative to liver transplantation

Kren

Chowdhury

et al. 2002

Liver Transplantation

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Liver transplantation has become a well-recognized therapy for hepatic failure resulting from acute or chronic liver disease. It also plays a role in the treatment of certain inborn errors of metabolism that do not directly injure the liver. In fact, the liver maintains a central role in many inherited and acquired genetic disorders. There has been a considerable effort to develop new and more effective gene therapy approaches, in part, to overcome the need for transplantation as well as the shortage of donor livers. Traditional gene therapy involves the delivery of a piece of DNA to replace the faulty gene. More recently, there has been a growing interest in the use of gene repair to correct certain genetic defects. In fact, targeted gene repair has many advantages over conventional replacement strategies. In this review, we will describe a variety of viral and nonviral strategies that are now available to the liver. The ever-growing list includes viral vectors, antisense and ribozyme technology, and the Sleeping Beauty transposon system. In addition, targeted gene repair with RNA/DNA oligonucleotides, small-fragment homologous replacement, and triplex-forming and single-stranded oligonucleotides is a long-awaited and potentially exciting approach. Although each method uses different mechanisms for gene repair and therapy, they all share a basic requirement for the efficient delivery of DNA. (Liver

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RNA facilitates RecA-mediated DNA pairing and strand transfer between molecules bearing limited regions of homology

Cited by 18 publications

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α2p controls donor preference during mating type interconversion in yeast by inactivating a recombinational enhancer of chromosome III

α2p controls donor preference during mating type interconversion in yeast by inactivating a recombinational enhancer of chromosome III

Prospects of chimeric RNA-DNA oligonucleotides in gene therapy

Gene therapy as an alternative to liver transplantation

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