Cloning and sequencing of the PIF gene involved in repair and recombination of yeast mitochondrial DNA.

Foury, Françoise; Lahaye, A.

doi:10.1002/j.1460-2075.1987.tb02385.x

Cited by 106 publications

(66 citation statements)

References 46 publications

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“…Consistent with this idea is that yeast mitochondria contain at least two proteins implicated in mtDNA recombination, Pif1p, a DNA helicase (24), and Mhr1p, a protein of unknown function, both of which appear to be also involved in mtDNA repair or damage tolerance (17,18,28). In addition, Msh1p, a homolog of the bacterial mismatch repair protein MutS, is localized to and functions in mitochondria (5).…”

mentioning

confidence: 99%

Mitochondrial Dysfunction Due to Oxidative Mitochondrial DNA Damage Is Reduced through Cooperative Actions of Diverse Proteins

O'Rourke

Doudican

Mackereth

et al. 2002

Molecular and Cellular Biology

116

114

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The mitochondrial genome is a significant target of exogenous and endogenous genotoxic agents; however, the determinants that govern this susceptibility and the pathways available to resist mitochondrial DNA (mtDNA) damage are not well characterized. Here we report that oxidative mtDNA damage is elevated in strains lacking Ntg1p, providing the first direct functional evidence that this mitochondrion-localized, base excision repair enzyme functions to protect mtDNA. However, ntg1 null strains did not exhibit a mitochondrial respiration-deficient (petite) phenotype, suggesting that mtDNA damage is negotiated by the cooperative actions of multiple damage resistance pathways. Null mutations in ABF2 or PIF1, two genes implicated in mtDNA maintenance and recombination, exhibit a synthetic-petite phenotype in combination with ntg1 null mutations that is accompanied by enhanced mtDNA point mutagenesis in the corresponding double-mutant strains. This phenotype was partially rescued by malonic acid, indicating that reactive oxygen species generated by the electron transport chain contribute to mitochondrial dysfunction in abf2⌬ strains. In contrast, when two other genes involved in mtDNA recombination, CCE1 and NUC1, were inactivated a strong synthetic-petite phenotype was not observed, suggesting that the effects mediated by Abf2p and Pif1p are due to novel activities of these proteins other than recombination. These results document the existence of recombination-independent mechanisms in addition to base excision repair to cope with oxidative mtDNA damage in Saccharomyces cerevisiae. Such systems are likely relevant to those operating in human cells where mtDNA recombination is less prevalent, validating yeast as a model system in which to study these important issues.Mitochondria are important cellular targets for spontaneous and induced DNA damage (3,7,36,38,43), and mutations in mitochondrial DNA (mtDNA) cause diseases and likely contribute to late-onset neurodegenerative disorders and the aging process in humans (25, 51). Oxidative damage persists longer in mtDNA than it does in nuclear DNA (52) and appears to be a major contributor to mtDNA mutagenesis in vivo. In addition, decreased mitochondrial oxidative phosphorylation capacity is linked to oxidative stress pathways that perturb other cellular components and functions (52). The susceptibility of mtDNA to oxidative damage has been hypothesized to arise from a combination of biological determinants (36), including the proximity of mtDNA to reactive oxygen species that are by-products of normal respiration, the lack of a compact nucleosome structure to protect mtDNA from damage, and a paucity of mtDNA damage-processing pathways relative to those known to exist in the nucleus (6). However, it is largely unknown if and how these factors ultimately contribute to the susceptibility of mtDNA to damage.DNA damage caused by reactive oxygen species is removed by the base excision repair pathway (32), which is initiated by the action of glycosylases that excise specific d...

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mentioning

confidence: 99%

Mitochondrial Dysfunction Due to Oxidative Mitochondrial DNA Damage Is Reduced through Cooperative Actions of Diverse Proteins

O'Rourke

Doudican

Mackereth

et al. 2002

Molecular and Cellular Biology

116

114

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“…cerevisiae and Sch. pombe, where it has been shown to be involved in repair and recombination of mitochondrial DNA (mtDNA) (Foury & Lahaye, 1987), chromosomal DNA replication (Ivessa et al, 2000;Zhou et al, 2002), and maintenance of telomeres and rDNA (Ivessa et al, 2000;Schulz & Zakian, 1994). PIF1 is not essential during the vegetative growth of Sac.…”

Section: Discussionmentioning

confidence: 99%

“…Functional complementation of R2427 has been achieved using the wild-type C. minitans gene. In other fungi, PIF1 is involved in mitochondrial DNA (mtDNA) repair and recombination and has a role in the maintenance of mitochondria in response to oxidative stress (Doudican et al, 2005;Foury & Lahaye, 1987). This paper describes molecular characterization of the C. minitans PIF1 gene and demonstrates its concomitant role in mycelial growth and sclerotial mycoparasitism.…”

Section: Introductionmentioning

confidence: 98%

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Disruption of the Coniothyrium minitans PIF1 DNA helicase gene impairs growth and capacity for sclerotial mycoparasitism

et al. 2008

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A non-mycoparasitic restriction enzyme-mediated DNA integration (REMI) mutant of Coniothyrium minitans (R2427) contains two tandem plasmid copies integrated towards the 39 end of an ORF. The predicted polypeptide (845 aa) exhibits high similarity with DNA-helicase proteins from other filamentous fungi and yeasts that play a role in mitochondrial DNA maintenance and repair. Disruption of the C. minitans PIF1 DNA helicase gene results in altered morphology, reduced growth rates and a concomitant loss in ability to mycoparasitize sclerotia of Sclerotinia sclerotiorum. In infection bioassays, R2427 exhibited sparse mycelial growth on the surface of live sclerotia, but no mycelia were detected inside the sclerotia. Conversely, R2427 readily colonized autoclaved sclerotia. Complementation of the mutant with wild-type PIF1 restored normal mycelial growth and mycoparasitic capability, confirming a functional role in the host-pathogen interaction. The C. minitans PIF1 DNA helicase may maintain mitochondrial stability in response to reactive oxygen species, either produced endogenously within the mycoparasite, or exogenously from the sclerotial host.

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“…Place Jussieu, F-75251, Pans, France mitochondrial endonucleases that closely resemble the bovine endonuclease have been partially purified and characterized from rat and human heart mitochondria (Low et al, 1988). Recent evidence suggests that rccornbination may occur in mitochondria, particulary within duplicated sequences (Foury and Lahaye, 1987;Dieckmann and Gandy, 1987;Ahne et al, 1988;Gross et al, 1984;Almasan and Mishra, 1988;Turker et al, 1987). It is possible, therefore, that the mitochondrial endonuclcasc described here participates in either mitochondrial DNA recombination, repair and/or replication.…”

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confidence: 99%

Purification and characterization of a mitochondrial endonuclease from Drosophila melanogaster embryos

Harosh

Mezzina

Harris

et al. 1992

European Journal of Biochemistry

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A mitochondrial endonuclease from Drosophila melanogaster embryos was purified to near homogeneity by successive fractionation with DEAE-cellulose and heparin -avidgel-F, followed by FPLC chromatography on mono S, Superose 12 and a second mono S column. This enzyme digests doublestranded DNA more efficiently than heat-denatured DNA. The endonuclease activity has a molecular mass of 44 kDa, as determined under native conditions using a gel-filtration Superose 12 column. The prominent peptide detected by SDS/polyacrylamide gel electrophoresis likewise has a molecular mass of 44 kDa, suggesting a monomeric protein. The enzyme has an absolute requirement for divalent cations, preferring MgZf over Mn2+. No activity could be detected when these cations were replaced by Ca2+ or Zn2+. The pH optimum for this enzyme activity is 6.5-7.4 and its isoelectric point is 4.9. Both single-strand and double-strand breaks are introduced simultaneously into a supercoiled substrate in the presence of MgClz or MnCl,. Endonuclease-treated DNA serves as a substrate for DNA polymerase I from Escherichiu coli, suggesting that 3'-OH termini are generated during cleavage. The enzyme is free from any detectable DNA exonuclease activity but not from RNase activity. Partial inhibition by antibodies raised against mitochondrial endonucleases derived from bovine heart and Saccharom yces cerevisia have revealed a potential structural homology between these nucleases.

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Cloning and sequencing of the PIF gene involved in repair and recombination of yeast mitochondrial DNA.

Cited by 106 publications

References 46 publications

Mitochondrial Dysfunction Due to Oxidative Mitochondrial DNA Damage Is Reduced through Cooperative Actions of Diverse Proteins

Mitochondrial Dysfunction Due to Oxidative Mitochondrial DNA Damage Is Reduced through Cooperative Actions of Diverse Proteins

Disruption of the Coniothyrium minitans PIF1 DNA helicase gene impairs growth and capacity for sclerotial mycoparasitism

Purification and characterization of a mitochondrial endonuclease from Drosophila melanogaster embryos

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