Mitochondrial DNA repairs double-strand breaks in yeast chromosomes

Ricchetti, Miria; Fairhead, Cécile; Dujon, Bernard

doi:10.1038/47076

Cited by 242 publications

(253 citation statements)

References 26 publications

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“…The insertion of organelle DNA at sites of DSB repair in yeast was first reported more than a decade ago (37). Although indirect evidence of the same process occurring in some higher organisms has been published (17,38), the present study has been able to demonstrate directly that organelle DNA integrates at DSBs in multicellular eukaryotes.…”

Section: Discussionsupporting

confidence: 54%

Environmental stress increases the entry of cytoplasmic organellar DNA into the nucleus in plants

Wang

Lloyd

Timmis

2012

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

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Mitochondria and chloroplasts (photosynthetic members of the plastid family of cytoplasmic organelles) in eukaryotic cells originated more than a billion years ago when an ancestor of the nucleated cell engulfed two different prokaryotes in separate sequential events. Extant cytoplasmic organellar genomes contain very few genes compared with their candidate free-living ancestors, as most have functionally relocated to the nucleus. The first step in functional relocation involves the integration of inactive DNA fragments into nuclear chromosomes, and this process continues at high frequency with attendant genetic, genomic, and evolutionary consequences. Using two different transplastomic tobacco lines, we show that DNA migration from chloroplasts to the nucleus is markedly increased by mild heat stress. In addition, we show that insertion of mitochondrial DNA fragments during the repair of induced double-strand breaks is increased by heat stress. The experiments demonstrate that the nuclear influx of organellar DNA is a potentially a source of mutation for nuclear genomes that is highly susceptible to temperature fluctuations that are well within the range experienced naturally.D NA in the highly energetic cytoplasmic organellar genetic compartments of eukaryotes is subjected to high levels of stress damage from the oxygen free radicals produced during respiration and photosynthesis. Nonetheless, for various reasons, the rate of accumulation of mutations is slower in plant cytoplasmic organelles than in the nucleus (1, 2). The vast majority of mitochondrial and plastid (chloroplast) genes have vacated their ancestral prokaryote genetic compartment in favor of the nucleus (2), with very few remaining within extant organelles. The first step in gene relocation for the organelle genomes is DNA escape, followed by insertion into nuclear chromosomes, a process shown to occur remarkably frequently under normal physiological conditions in tobacco (3, 4) and yeast (5), although an experimental screen in the unicellular alga Chlamydomonas reinhardtii did not detect any such transpositions (6). These experimental studies, together with bioinformatic and genomic analyses (7)(8)(9)(10)(11)(12)(13)(14), demonstrated that DNA transfer from cytoplasmic organelles is a frequent and continuous process in essentially all eukaryotes examined, although it may be very rare in organisms with very low organelle numbers (15). Although DNA transfer per se is very frequent in higher plants, genes that migrate are normally inactive in the nucleus because they lack the motifs required for nuclear expression. Nonetheless, on rare occasions nuclear integrants of organelle DNA (norgs) are activated by genomic rearrangements (16,17), that effectively duplicate the gene. Over evolutionary time, these frequent nonfunctional and rare functional DNA transfer processes have resulted in the net loss of redundant genes in the cytoplasmic organelles and have added to the genetic complexity of the nucleus.Environmental factors are known to modify mitoch...

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Section: Discussionsupporting

confidence: 54%

Environmental stress increases the entry of cytoplasmic organellar DNA into the nucleus in plants

Wang

Lloyd

Timmis

2012

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

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“…Similar microhomology (2-4 bp) was identified at mtDNA͞nuclear and mtDNA͞mtDNA junctions in yeast chromosomal DNA when double-strand breaks were introduced (2). The essentially random distribution of historically transferred mtDNA in the yeast genome (2) and mtDNA and ptDNA in rice chromosome 10 (6) argues against site-selective integration of organelle DNA.…”

Section: New Nupts Are Generally Larger Than the Transcripts Of Selecmentioning

confidence: 74%

“…The transfer of DNA fragments from captured ancestral prokaryotes to the eukaryotic host genome has led to the acquisition of thousands of erstwhile prokaryote genes by the nucleus and the diminution of organelle genomes to small remnants (1). Nonfunctional organelle DNA fragments are present in nearly all eukaryote nuclear genomes with some of the largest integrants representing entire chloroplast or mitochondrial genomes (2)(3)(4)(5)(6)(7). Sequence comparisons of nuclear and organelle genomes suggest that the transfer of organelle DNA is an ongoing process (1)(2)(3).…”

mentioning

confidence: 99%

Simple and complex nuclear loci created by newly transferred chloroplast DNA in tobacco

Huang

Ayliffe

Timmis

2004

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

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Transfer of organelle DNA into the nuclear genome has been significant in eukaryotic evolution, because it appears to be the origin of many nuclear genes. Most studies on organelle DNA transfer have been restricted to evolutionary events but experimental systems recently became available to monitor the process in real time. We designed an experimental screen to detect plastid DNA (ptDNA) transfers to the nucleus in whole plants grown under natural conditions. The resultant genotypes facilitated investigation of the evolutionary mechanisms underlying ptDNA transfer and nuclear integration. Here we report the characterization of nuclear loci formed by integration of newly transferred ptDNA. Large, often multiple, fragments of ptDNA between 6.0 and 22.3 kb in size are incorporated into chromosomes at single Mendelian loci. The lack of chloroplast transcripts of comparable size to the ptDNA integrants suggests that DNA molecules are directly involved in the transfer process. Microhomology (2-5 bp) and rearrangements of ptDNA and nuclear DNA were frequently found near integration sites, suggesting that nonhomologous recombination plays a major role in integration. The mechanisms of ptDNA integration appear similar to those of biolistic transformation of plant cells, but no sequence preference was identified near junctions. This article provides substantial molecular analysis of real-time ptDNA transfer and integration that has resulted from natural processes with no involvement of cell injury, infection, and tissue culture. We highlight the impact of cytoplasmic organellar genome mobility on nuclear genome evolution.

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“…During religation, exogenous DNA may be captured in the chromosome, leading to insertion of DNA into the genome. In eukaryotes, DNA inserted into the genome by NHEJ during evolution may include foreign DNA fragments such as mitochondrial DNA, transposable elements, and viral DNA (Moore and Haber 1996;Ricchetti et al 1999;Lin and Waldman 2001a;Lin and Waldman 2001b;Nakai et al 2003;Hazkani-Covo and Covo 2008). The classical eukaryotic NHEJ machinery includes the KU70/80 heterodimer (KU), XRCC4, Ligase IV, and DNA-PKcs proteins (Bassing and Alt 2004;Lieber et al 2004).…”

Section: Recent Lgt Between Distantly Related Speciesmentioning

confidence: 99%

Directed networks reveal genomic barriers and DNA repair bypasses to lateral gene transfer among prokaryotes

Popa

Hazkani‐Covo²,

Landan³

et al. 2011

Genome Res.

227

204

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Lateral gene transfer (LGT) plays a major role in prokaryote evolution with only a few genes that are resistant to it; yet the nature and magnitude of barriers to lateral transfer are still debated. Here, we implement directed networks to investigate donor-recipient events of recent lateral gene transfer among 657 sequenced prokaryote genomes. For 2,129,548 genes investigated, we detected 446,854 recent lateral gene transfer events through nucleotide pattern analysis. Among these, donor-recipient relationships could be specified through phylogenetic reconstruction for 7% of the pairs, yielding 32,028 polarized recent gene acquisition events, which constitute the edges of our directed networks. We find that the frequency of recent LGT is linearly correlated both with genome sequence similarity and with proteome similarity of donor-recipient pairs. Genome sequence similarity accounts for 25% of the variation in gene-transfer frequency, with proteome similarity adding only 1% to the variability explained. The range of donor-recipient GC content similarity within the network is extremely narrow, with 86% of the LGTs occurring between donor-recipient pairs having #5% difference in GC content. Hence, genome sequence similarity and GC content similarity are strong barriers to LGT in prokaryotes. But they are not insurmountable, as we detected 1530 recent transfers between distantly related genomes. The directed network revealed that recipient genomes of distant transfers encode proteins of nonhomologous end-joining (NHEJ; a DNA repair mechanism) far more frequently than the recipient lacking that mechanism. This implicates NHEJ in genes spread across distantly related prokaryotes through bypassing the donor-recipient sequence similarity barrier.

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Mitochondrial DNA repairs double-strand breaks in yeast chromosomes

Cited by 242 publications

References 26 publications

Environmental stress increases the entry of cytoplasmic organellar DNA into the nucleus in plants

Environmental stress increases the entry of cytoplasmic organellar DNA into the nucleus in plants

Simple and complex nuclear loci created by newly transferred chloroplast DNA in tobacco

Directed networks reveal genomic barriers and DNA repair bypasses to lateral gene transfer among prokaryotes

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