Homologous Recombination in Plants: An Antireview

Lieberman‐Lazarovich, Michal; Levy, Avraham A.

doi:10.1007/978-1-61737-957-4_3

Cited by 38 publications

(22 citation statements)

References 76 publications

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“…While HR-mediated repair of mtDNA has been reported in plants and yeast, the occurrence of a bonafide HR repair mechanism in mammalian mitochondria has been debated and remains to be elucidated [121–125]. Some evidence for HR occurring within mammalian mitochondria was presented in studies using mitochondrial extracts where a recombinase RecA-mediated recombination event was observed [126].…”

Section: Mitochondrial Dna Genome Maintenancementioning

confidence: 99%

DNA damage related crosstalk between the nucleus and mitochondria

Saki

Prakash

2017

Free Radical Biology and Medicine

130

105

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The electron transport chain is the primary pathway by which a cell generates energy in the form of ATP. Byproducts of this process produce reactive oxygen species that can cause damage to mitochondrial DNA. If not properly repaired, the accumulation of DNA damage can lead to mitochondrial dysfunction linked to several human disorders including neurodegenerative diseases and cancer. Mitochondria are able to combat oxidative DNA damage via repair mechanisms that are analogous to those found in the nucleus. Of the repair pathways currently reported in the mitochondria, the base excision repair pathway is the most comprehensively described. Proteins that are involved with the maintenance of mtDNA are encoded by nuclear genes and translocate to the mitochondria making signaling between the nucleus and mitochondria imperative. In this review, we discuss the current understanding of mitochondrial DNA repair mechanisms and also highlight the sensors and signaling pathways that mediate crosstalk between the nucleus and mitochondria in the event of mitochondrial stress.

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Section: Mitochondrial Dna Genome Maintenancementioning

confidence: 99%

DNA damage related crosstalk between the nucleus and mitochondria

Saki

Prakash

2017

Free Radical Biology and Medicine

130

105

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“…plant biotechnology | plant breeding | gene technology | double-strand-break repair S ince the first report on gene targeting (GT) in plants was published (1), various approaches were tested to improve the efficiency of the method (2-5), which has been summarized in recent reviews (6,7). We were able to demonstrate that the integration of a transfer DNA (T-DNA) by homologous recombination (HR) into a specific locus could be enhanced by two orders of magnitude via double-strand-break (DSB) induction using a site-specific endonuclease (8).…”

mentioning

confidence: 99%

In planta gene targeting

Fauser

Roth

Pacher

et al. 2012

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

197

176

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The development of designed site-specific endonucleases boosted the establishment of gene targeting (GT) techniques in a row of different species. However, the methods described in plants require a highly efficient transformation and regeneration procedure and, therefore, can be applied to very few species. Here, we describe a highly efficient GT system that is suitable for all transformable plants regardless of transformation efficiency. Efficient in planta GT was achieved in Arabidopsis thaliana by expression of a sitespecific endonuclease that not only cuts within the target but also the chromosomal transgenic donor, leading to an excised targeting vector. Progeny clonal for the targeted allele could be obtained directly by harvesting seeds. Targeted events could be identified up to approximately once per 100 seeds depending on the target donor combination. Molecular analysis demonstrated that, in almost all events, homologous recombination occurred at both ends of the break. No ectopic integration of the GT vector was found.plant biotechnology | plant breeding | gene technology | double-strand-break repair S ince the first report on gene targeting (GT) in plants was published (1), various approaches were tested to improve the efficiency of the method (2-5), which has been summarized in recent reviews (6, 7). We were able to demonstrate that the integration of a transfer DNA (T-DNA) by homologous recombination (HR) into a specific locus could be enhanced by two orders of magnitude via double-strand-break (DSB) induction using a site-specific endonuclease (8). More recently, by the use of zinc finger nucleases (9), which, in principle, can be used to induce a DSB at any genomic site, endogenous loci have been targeted in Arabidopsis (10), tobacco (11), and maize (12) at high frequencies (13). Some time ago, a method for in vivo targeting was developed in Drosophila. A stably integrated donor precursor molecule is first circularized by the FLP recombinase and subsequently linearized via cutting a single I-SceI recognition site, generating the actual GT vector (14). However, such a technique has not been successfully transferred to plants. We have previously shown that DNA can be efficiently excised from the genome in planta by the use of a site-specific endonuclease (15). To test whether the combination of this approach with DSB-induced recombination might lead to an efficient GT system, that is independent of transformation, we performed a proof-of-concept (POC) experiment in Arabidopsis using I-SceI (16) as a sitespecific nuclease. ResultsGenerating Homozygous Single-Copy GT Lines. Our in planta GT system is based on three different constructs (two shown in Fig. 1A) that were transformed independently by floral dipping. The target locus contains a truncated β-glucuronidase (GUS) gene (uidA) that can be restored via GT. DSB induction at the two ISceI recognition sites flanking a kanamycin-resistance gene would result in excision of the kanamycin-resistance gene and in activation of the target locus for HR. Th...

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“…The basis of these experiments is that the double-strand cleavage of DNA induces the cells' repair machinery to correct the damaged molecule. By the help of the subsequent processes (i) the shifted reading frame can be restored or a random mutation can be induced for gene knockout purpose by non-homologous end-joining, or (ii) a DNA of erroneous sequence -causing a genetic disease -can be corrected, or a gene can be inserted in a targeted way by homologous recombination in the presence of a suitable DNA template [12][13][14][15][16][17][18][19][20][21]. Because of this large scientific potential, there is a high demand of constructing specific artificial nucleases, as it is demonstrated by the continuously increasing number of publications on this hot topic.…”

Section: Introductionmentioning

confidence: 99%

Rescue of the activity of HNH nuclease mutants - towards controlled enzymes for gene therapy

Gyurcsik

2016

CPPS

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Artificial nucleases are designed for in vivo gene engineering, as the DNA cleavage performed at a specific target site enhances the effectiveness of the cell's DNA repair machinery. The therapeutic potential of the above phenomenon stems from the knowledge that (i) the shifted reading frame can be restored by non-homologous end-joining, or (ii) a DNA of erroneous sequence -causing a genetic disease -can be corrected by homologous recombination in the presence of a suitable DNA template. Besides the advantageous properties of the nowadays applied zinc finger nucleases, TALE nucleases and the CRISPR/Cas9 system, they possess a residual citotoxicity. This is related to offtarget cleavages, which could be prevented by the strict regulation of the enzymes. The studies on enzymes acting naturally in a controlled manner are beneficial to get better insight into their mechanism. Such enzymes or their appropriate domains may be the most promising alternatives to the presently applied ones. As an example, the DNA cleavage of the inactive HNH nuclease mutants is inducible in a multiple way. This property may be used for establishing a control mechanism and thus, in combination with specific DNA-binding domains they are good candidates for the catalytic site of artificial nucleases. Here we collect the results on the properties of the HNH nucleases that allow for their redesign into enzymes with possible therapeutic applications.

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Homologous Recombination in Plants: An Antireview

Cited by 38 publications

References 76 publications

DNA damage related crosstalk between the nucleus and mitochondria

DNA damage related crosstalk between the nucleus and mitochondria

In planta gene targeting

Rescue of the activity of HNH nuclease mutants - towards controlled enzymes for gene therapy

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