J. Cell Biol., Volume 145, Number 2, April 19, 1999 291-304

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

Shelly Meeusen,^* Quinton Tieu,^* Edith Wong,^* Eric Weiss,^* David Schieltz, John R. Yates, and Jodi Nunnari^*

^* Section of Molecular and Cellular Biology, University of California, Davis, California 95616; and  The Department of Molecular Biotechnology, University of Washington, School of Medicine, Seattle, Washington 98195

Maintenance of mitochondrial DNA (mtDNA) during cell division is required for progeny to be respiratory competent. Maintenance involves the replication, repair, assembly, segregation, and partitioning of the mitochondrial nucleoid. MGM101 has been identified as a gene essential for mtDNA maintenance in S. cerevisiae, but its role is unknown. Using liquid chromatography coupled with tandem mass spectrometry, we identified Mgm101p as a component of highly enriched nucleoids, suggesting that it plays a nucleoid-specific role in maintenance. Subcellular fractionation, indirect immunofluorescence and GFP tagging show that Mgm101p is exclusively associated with the mitochondrial nucleoid structure in cells. Furthermore, DNA affinity chromatography of nucleoid extracts indicates that Mgm101p binds to DNA, suggesting that its nucleoid localization is in part due to this activity. Phenotypic analysis of cells containing a temperature sensitive mgm101 allele suggests that Mgm101p is not involved in mtDNA packaging, segregation, partitioning or required for ongoing mtDNA replication. We examined Mgm101p's role in mtDNA repair. As compared with wild-type cells, mgm101 cells were more sensitive to mtDNA damage induced by UV irradiation and were hypersensitive to mtDNA damage induced by gamma rays and H₂O₂ treatment. Thus, we propose that Mgm101p performs an essential function in the repair of oxidatively damaged mtDNA that is required for the maintenance of the mitochondrial genome.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Lavoie, H., Whiteway, M. (2008). Increased Respiration in the sch9{Delta} Mutant Is Required for Increasing Chronological Life Span but Not Replicative Life Span. Eukaryot Cell 7: 1127-1135 [Abstract] [Full Text]  
• Chen, X. J., Wang, X., Butow, R. A. (2007). Yeast aconitase binds and provides metabolically coupled protection to mitochondrial DNA. Proc. Natl. Acad. Sci. USA 104: 13738-13743 [Abstract] [Full Text]  
• Lu, B., Yadav, S., Shah, P. G., Liu, T., Tian, B., Pukszta, S., Villaluna, N., Kutejova, E., Newlon, C. S., Santos, J. H., Suzuki, C. K. (2007). Roles for the Human ATP-dependent Lon Protease in Mitochondrial DNA Maintenance. J. Biol. Chem. 282: 17363-17374 [Abstract] [Full Text]  
• Wang, Y., Bogenhagen, D. F. (2006). Human Mitochondrial DNA Nucleoids Are Linked to Protein Folding Machinery and Metabolic Enzymes at the Mitochondrial Inner Membrane. J. Biol. Chem. 281: 25791-25802 [Abstract] [Full Text]  
• Nishimura, Y., Yoshinari, T., Naruse, K., Yamada, T., Sumi, K., Mitani, H., Higashiyama, T., Kuroiwa, T. (2006). Active digestion of sperm mitochondrial DNA in single living sperm revealed by optical tweezers. Proc. Natl. Acad. Sci. USA 103: 1382-1387 [Abstract] [Full Text]  
• Dai, H., Lo, Y.-S., Litvinchuk, A., Wang, Y.-T., Jane, W.-N., Hsiao, L.-J., Chiang, K.-S. (2005). Structural and functional characterizations of mung bean mitochondrial nucleoids. Nucleic Acids Res 33: 4725-4739 [Abstract] [Full Text]  
• Chen, X. J., Wang, X., Kaufman, B. A., Butow, R. A. (2005). Aconitase Couples Metabolic Regulation to Mitochondrial DNA Maintenance. Science 307: 714-717 [Abstract] [Full Text]  
• Coene, E. D., Hollinshead, M. S., Waeytens, A. A.T., Schelfhout, V. R.J., Eechaute, W. P., Shaw, M. K., Van Oostveldt, P. M.V., Vaux, D. J. (2005). Phosphorylated BRCA1 Is Predominantly Located in the Nucleus and Mitochondria. Mol. Biol. Cell 16: 997-1010 [Abstract] [Full Text]  
• Guo, J., Lemire, B. D. (2003). The Ubiquinone-binding Site of the Saccharomyces cerevisiae Succinate-Ubiquinone Oxidoreductase Is a Source of Superoxide. J. Biol. Chem. 278: 47629-47635 [Abstract] [Full Text]  
• Meeusen, S., Nunnari, J. (2003). Evidence for a two membrane-spanning autonomous mitochondrial DNA replisome. J. Cell Biol. 163: 503-510 [Abstract] [Full Text]  
• Wong, E. D., Wagner, J. A., Scott, S. V., Okreglak, V., Holewinske, T. J., Cassidy-Stone, A., Nunnari, J. (2003). The intramitochondrial dynamin-related GTPase, Mgm1p, is a component of a protein complex that mediates mitochondrial fusion. J. Cell Biol. 160: 303-311 [Abstract] [Full Text]  
• Bateman, J. M., Perlman, P. S., Butow, R. A. (2002). Mutational Bisection of the Mitochondrial DNA Stability and Amino Acid Biosynthetic Functions of Ilv5p of Budding Yeast. Genetics 161: 1043-1052 [Abstract] [Full Text]  
• Zuo, X. M., Clark-Walker, G. D., Chen, X. J. (2002). The Mitochondrial Nucleoid Protein, Mgm101p, of Saccharomyces cerevisiae Is Involved in the Maintenance of {rho}+ and ori/rep-Devoid Petite Genomes but Is Not Required for Hypersuppressive {rho}- mtDNA. Genetics 160: 1389-1400 [Abstract] [Full Text]  
• Wong, E. D., Wagner, J. A., Gorsich, S. W., McCaffery, J. M., Shaw, J. M., Nunnari, J. (2000). The Dynamin-related GTPase, Mgm1p, Is an Intermembrane Space Protein Required for Maintenance of Fusion Competent Mitochondria. J. Cell Biol. 151: 341-352 [Abstract] [Full Text]  
• Tieu, Q., Nunnari, J. (2000). Mdv1p Is a WD Repeat Protein that Interacts with the Dynamin-related GTPase, Dnm1p, to Trigger Mitochondrial Division. J. Cell Biol. 151: 353-366 [Abstract] [Full Text]  
• Oxelmark, E., Marchini, A., Malanchi, I., Magherini, F., Jaquet, L., Hajibagheri, M. A. N., Blight, K. J., Jauniaux, J.-C., Tommasino, M. (2000). Mmf1p, a Novel Yeast Mitochondrial Protein Conserved throughout Evolution and Involved in Maintenance of the Mitochondrial Genome. Mol. Cell. Biol. 20: 7784-7797 [Abstract] [Full Text]  
• Kaufman, B. A., Newman, S. M., Hallberg, R. L., Slaughter, C. A., Perlman, P. S., Butow, R. A. (2000). In organello formaldehyde crosslinking of proteins to mtDNA: Identification of bifunctional proteins. Proc. Natl. Acad. Sci. USA 10.1073/pnas.140063197v1 [Abstract] [Full Text]  
• Contamine, V., Picard, M. (2000). Maintenance and Integrity of the Mitochondrial Genome: a Plethora of Nuclear Genes in the Budding Yeast. Microbiol. Mol. Biol. Rev. 64: 281-315 [Abstract] [Full Text]  
• Kaufman, B. A., Newman, S. M., Hallberg, R. L., Slaughter, C. A., Perlman, P. S., Butow, R. A. (2000). In organello formaldehyde crosslinking of proteins to mtDNA: Identification of bifunctional proteins. Proc. Natl. Acad. Sci. USA 97: 7772-7777 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents