Mgm101p Is a Novel Component of the Mitochondrial Nucleoid That Binds DNA and Is Required for the Repair of Oxidatively Damaged Mitochondrial DNA

Meeusen, Shelly; Tieu, Quinton; Wong, Edith D.; Weiss, Eric L.; Schieltz, David; Yates, John R.; Nunnari, Jodi

doi:10.1083/jcb.145.2.291

Cited by 93 publications

(89 citation statements)

References 53 publications

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“…Together with the hypersensitivity of the mgm101 N150A mutant to hydrogen peroxide and other DNAdamaging agents (26), the data strongly support a role of the protein in recombinational repair in vivo. Recombination between non-tandem direct repeats generally results from recombinational repair of dsDNA breaks, which are mediated either by non-allelic strand invasion between the repeats or by annealing of non-allelic repeated sequences after exonuclease resection of dsDNA breaks.…”

Section: Discussionmentioning

confidence: 57%

“…Mature Mgm101 is a positively charged protein of 247 amino acids (25). Nunnari and co-workers (26,27) have shown that Mgm101 is associated with actively replicating mitochondrial nucleoids and that mtDNA in mgm101 mutants is hypersensitive to several DNA-damaging agents, including ultraviolet, ␥-ray irradiation, and hydrogen peroxide. These observations strongly suggested a role for Mgm101 in mtDNA repair.…”

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confidence: 99%

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Mgm101 Is a Rad52-related Protein Required for Mitochondrial DNA Recombination

Mbantenkhu

Wang

Nardozzi

et al. 2011

Journal of Biological Chemistry

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Background:The mechanisms of homologous recombination and recombinational repair of double-stranded DNA breaks in mitochondria are poorly understood. Results: The yeast mitochondrial nucleoid protein, Mgm101, shares biochemical, structural, and functional similarities with the Rad52 family proteins. Conclusion: Mgm101 is a Rad52-related molecular component involved in mtDNA recombination Significance: This finding helps in understanding the mechanism of homologous recombination in mitochondria.

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Section: Discussionmentioning

confidence: 57%

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confidence: 99%

Mgm101 Is a Rad52-related Protein Required for Mitochondrial DNA Recombination

Mbantenkhu

Wang

Nardozzi

et al. 2011

Journal of Biological Chemistry

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“…A number of mt (cp) nucleoid proteins have been identified in yeast (39)(40)(41)(42), algae (43), and plants (44,45). An intriguing example of a mt nucleoid protein is Glom, which is a structural nucleoid protein that also maintains the replication and transcriptional activity of mtDNA in slime mold (46).…”

Section: Discussionmentioning

confidence: 99%

Active digestion of sperm mitochondrial DNA in single living sperm revealed by optical tweezers

Nishimura

Yoshinari

Naruse

et al. 2006

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

146

104

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In almost all eukaryotes, mitochondrial (mt) genes are transmitted to progeny mainly from the maternal parent. The most popular explanation for this phenomenon is simple dilution of paternal mtDNA, because the paternal gametes (sperm) are much smaller than maternal gametes (egg) and contribute a limited amount of mitochondria to the progeny. Recently, this simple explanation has been challenged in several reports that describe the active digestion of sperm mtDNA, down-regulation of mtDNA replication in sperm, and proteolysis of mitochondria triggered by ubiquitination. In this investigation, we visualized mt nucleoids in living sperm by using highly sensitive SYBR green I vital staining. The ability to visualize mt nucleoids allowed us to clarify that the elimination of sperm mtDNA upon fertilization is achieved through two steps: (i) gradual decrease of mt nucleoid numbers during spermatogenesis and (ii) rapid digestion of sperm mtDNA just after fertilization. One notable point is that the digestion of mtDNA is achieved before the complete destruction of mitochondrial structures, which may be necessary to avoid the diffusion and transmission of potentially deleterious sperm mtDNA to the progeny. maternal inheritance ͉ medaka ͉ mtDNA M itochondria and chloroplasts contain their own genomes, which are believed to be vestiges of their bacterial ancestors (1). Mitochondrial (mt) and chloroplast (cp) genes are inherited in non-Mendelian fashion. A variety of patterns and mechanisms have been observed for the transmission of these genes, but in almost all eukaryotes, they are inherited mainly from the maternal parent (2-4).Generally, the maternal inheritance of mt (cp) DNA is thought to be a result of the dilution of the paternal contribution, because the paternal gametes (sperm) are much smaller than maternal gametes (egg) and contribute only a limited amount of cytoplasm to the progeny. In animals, a mature sperm carries Ϸ100 copies of mtDNA, which might be necessary to maintain the integrity of mitochondrial activity (5). In contrast, the animal oocyte contains Ϸ10 5 to 10 8 copies of mtDNA, exceeding that of sperm by a factor of at least 10 3 (3, 6). Therefore, the paternal contribution of mtDNA or cpDNA would be diluted beyond the limits of detection by using conventional restriction enzyme analysis (7).This simple explanation, however, has been challenged by many findings (8). For example, there have been several fairly unsuccessful attempts to detect leaky transmission of paternal mtDNA by repetitive backcross experiments using lepidopteran insects (9). On the contrary, in mussels (Mtylus), paternal mtDNA can be transmitted to male progeny at a remarkably high frequency, even though paternal mtDNAs are transmitted by sperm (10-12). A more striking example was found in the unicellular alga Chlamydomonas reinhardtii. In C. reinhardtii, despite the fact that mtϩ (female) and mtϪ (male) gametes contribute equal amounts of cytoplasm to the progeny, cpDNA is transmitted only from the mtϩ parent. One biochemical stud...

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“…By this method, roughly 20 polypeptide species are enriched, but only a few of them have been identified. Known nucleoid proteins include Abf2p, an abundant, high-mobility group protein required for the stability of wild-type ( ϩ ) mtDNA in cells grown on fermentable carbon sources (4), as well as for efficient mtDNA recombination (5,6), and Mgm101p, a protein possibly involved in mtDNA repair that is also required for the stability of ϩ mtDNA (7,8). Cells lacking Abf2p can maintain ϩ mtDNA when grown on nonfermentable carbon sources, and based on morphological and biochemical criteria, the mtDNA is organized differently than in wild-type cells (2,5).…”

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confidence: 99%

In organello formaldehyde crosslinking of proteins to mtDNA: Identification of bifunctional proteins

Kaufman

Newman

Hallberg

et al. 2000

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

186

139

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The segregating unit of mtDNA is a protein-DNA complex called the nucleoid. In an effort to understand how nucleoid proteins contribute to mtDNA organization and inheritance, we have developed an in organello formaldehyde crosslinking procedure to identify proteins associated with mtDNA. Using highly purified mitochondria, we observed a time-dependent crosslinking of protein to mtDNA as determined by sedimentation through isopycnic cesium chloride gradients. We detected Ϸ20 proteins crosslinked to mtDNA and identified 11, mostly by mass spectrometry. Among them is Abf2p, an abundant, high-mobility group protein that is known to function in nucleoid morphology, and in mtDNA transactions. In addition to several other proteins with known DNA binding properties or that function in mtDNA maintenance, we identified other mtDNA-associated proteins that were not anticipated, such as the molecular chaperone Hsp60p and a Krebs cycle protein, Kgd2p. Genetic experiments indicate that hsp60-ts mutants have a petite-inducing phenotype at the permissive temperature and that a kgd2⌬ mutation increases the petite-inducing phenotype of an abf2⌬ mutation. Crosslinking and DNA gel shift experiments show that Hsp60p binds to single-stranded DNA with high specificity for the template strand of a putative origin of mtDNA replication. These data identify bifunctional proteins that participate in the stability of ؉ mtDNA.

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Mgm101p Is a Novel Component of the Mitochondrial Nucleoid That Binds DNA and Is Required for the Repair of Oxidatively Damaged Mitochondrial DNA

Cited by 93 publications

References 53 publications

Mgm101 Is a Rad52-related Protein Required for Mitochondrial DNA Recombination

Mgm101 Is a Rad52-related Protein Required for Mitochondrial DNA Recombination

Active digestion of sperm mitochondrial DNA in single living sperm revealed by optical tweezers

In organello formaldehyde crosslinking of proteins to mtDNA: Identification of bifunctional proteins

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