Biochemical and genetic characterization of Hmi1p, a yeast DNA helicase involved in the maintenance of mitochondrial DNA

Monroe, Danny S.; Leitzel, Adelaide K.; Klein, Hannah L.; Matson, Steven W.

doi:10.1002/yea.1313

Cited by 14 publications

(6 citation statements)

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“…Alternatively, the single-stranded flap could be generated through helicase action. The Hmi1 helicase has the correct directionality (3Ј-5Ј) to generate substrates for Exo5, and it is also essential for maintenance of the wild-type mitochondrial genome but not for that of [rho Ϫ ] petites (21,26). Unfortunately, very little is known about the mechanism of replication of the yeast mitochondrial genome.…”

Section: Discussionmentioning

confidence: 99%

Yeast Exonuclease 5 Is Essential for Mitochondrial Genome Maintenance

Burgers

Stith

Yoder

et al. 2010

Molecular and Cellular Biology

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Yeast exonuclease 5 is encoded by the YBR163w (DEM1) gene, and this gene has been renamed EXO5. It is distantly related to the Escherichia coli RecB exonuclease class. Exo5 is localized to the mitochondria, and EXO5 deletions or nuclease-defective EXO5 mutants invariably yield petites, amplifying either the ori3 or ori5 region of the mitochondrial genome. These petites remain unstable and undergo continuous rearrangement. The mitochondrial phenotype of exo5⌬ strains suggests an essential role for the enzyme in DNA replication and recombination. No nuclear phenotype associated with EXO5 deletions has been detected. Exo5 is a monomeric 5 exonuclease that releases dinucleotides as products. It is specific for single-stranded DNA and does not hydrolyze RNA. However, Exo5 has the capacity to slide across 5 double-stranded DNA or 5 RNA sequences and resumes cutting two nucleotides downstream of the double-stranded-to-single-stranded junction or RNAto-DNA junction, respectively.Endonucleases and exonucleases are intimately involved in all aspects of DNA metabolism in the cell. In mitochondria, several constitutive nucleases have been identified that contribute to the proper maintenance of the mitochondrial genome through replication and recombination pathways. In addition, nucleases can localize to mitochondria in response to DNA stress in order to mediate appropriate DNA repair. Among the constitutive mitochondrial nucleases in Saccharomyces cerevisiae are the Nuc1 nuclease that contributes to DNA recombination efficiency and functions in apoptosis (4, 38) and the Cce1 endonuclease that resolves recombination intermediates (29). The Din7 endonuclease is a mitochondrially located 5Ј flap endonuclease related to FEN1 (20). While deletion of the gene for either of these enzymes produced marginal mitochondrial phenotypes, more severe phenotypes were observed when combined deletions of these nuclease genes were studied or when they were combined with deletions of other genes involved in DNA recombination or repair, such as MHR1 or MSH1 (20,22,27). Recently, human Dna2 was shown to localize to both the nuclear and mitochondrial compartments and to participate in mitochondrial DNA replication and base excision repair (11,39). Its function in yeast mitochondrial DNA maintenance has not been studied in detail. Finally, the 5Ј flap endonuclease FEN1, which normally functions in primer RNA degradation during Okazaki fragment maturation in the nucleus, also localizes to the mitochondrion in response to DNA damage, participating in long-patch base excision repair (19,23).Since mitochondrial function is not essential to yeast survival, dysfunction caused by mutations of the mitochondrial genome can be readily detected as a loss of respiration function, which is scored as the inability to grow on nonfermentable carbon sources. A defect in the mitochondrial DNA polymerase ␥ MIP1 results in complete loss of the mitochondrial DNA, and the mutant fails to grow on glycerol-containing media lacking glucose (14). Such cells are designated ...

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Section: Discussionmentioning

confidence: 99%

Yeast Exonuclease 5 Is Essential for Mitochondrial Genome Maintenance

Burgers

Stith

Yoder

et al. 2010

Molecular and Cellular Biology

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“…Hmi1 functionally overlaps with the Pif1 helicase with regard to the maintenance of some Ϫ genomes (106). One report showed that the helicase activity of Hmi1 is not essential for its mtDNA maintenance function (108). The nature of this cryptic function remains unsettled.…”

Section: Figmentioning

confidence: 99%

Mechanism of Homologous Recombination and Implications for Aging-Related Deletions in Mitochondrial DNA

Chen

2013

Microbiol Mol Biol Rev

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SUMMARY Homologous recombination is a universal process, conserved from bacteriophage to human, which is important for the repair of double-strand DNA breaks. Recombination in mitochondrial DNA (mtDNA) was documented more than 4 decades ago, but the underlying molecular mechanism has remained elusive. Recent studies have revealed the presence of a Rad52-type recombination system of bacteriophage origin in mitochondria, which operates by a single-strand annealing mechanism independent of the canonical RecA/Rad51-type recombinases. Increasing evidence supports the notion that, like in bacteriophages, mtDNA inheritance is a coordinated interplay between recombination, repair, and replication. These findings could have profound implications for understanding the mechanism of mtDNA inheritance and the generation of mtDNA deletions in aging cells.

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“…For instance, the gene HMI1 was found to be a DNA helicase and experimental results indicated that it localized in the mitochondria and was required for the maintenance of the functional mitochondrial genome [35]. The unwinding activity of the helicase requires ATP hydrolysis and has a 3′ to 5′ polarity [36]. Another gene in the subnetwork is YNL208W .…”

Section: Resultsmentioning

confidence: 99%

Enabling dynamic network analysis through visualization in TVNViewer

et al. 2012

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BackgroundMany biological processes are context-dependent or temporally specific. As a result, relationships between molecular constituents evolve across time and environments. While cutting-edge machine learning techniques can recover these networks, exploring and interpreting the rewiring behavior is challenging. Information visualization shines in this type of exploratory analysis, motivating the development ofTVNViewer (http://sailing.cs.cmu.edu/tvnviewer), a visualization tool for dynamic network analysis.ResultsIn this paper, we demonstrate visualization techniques for dynamic network analysis by using TVNViewer to analyze yeast cell cycle and breast cancer progression datasets.ConclusionsTVNViewer is a powerful new visualization tool for the analysis of biological networks that change across time or space.

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Biochemical and genetic characterization of Hmi1p, a yeast DNA helicase involved in the maintenance of mitochondrial DNA

Cited by 14 publications

References 58 publications

Yeast Exonuclease 5 Is Essential for Mitochondrial Genome Maintenance

Yeast Exonuclease 5 Is Essential for Mitochondrial Genome Maintenance

Mechanism of Homologous Recombination and Implications for Aging-Related Deletions in Mitochondrial DNA

Enabling dynamic network analysis through visualization in TVNViewer

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