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Nuclear Mitochondrial DNA Activates Replication in Saccharomyces cerevisiae

By Laurent Chatre and Miria Ricchetti


The nuclear genome of eukaryotes is colonized by DNA fragments of mitochondrial origin, called NUMTs. These insertions have been associated with a variety of germ-line diseases in humans. The significance of this uptake of potentially dangerous sequences into the nuclear genome is unclear. Here we provide functional evidence that sequences of mitochondrial origin promote nuclear DNA replication in Saccharomyces cerevisiae. We show that NUMTs are rich in key autonomously replicating sequence (ARS) consensus motifs, whose mutation results in the reduction or loss of DNA replication activity. Furthermore, 2D-gel analysis of the mrc1 mutant exposed to hydroxyurea shows that several NUMTs function as late chromosomal origins. We also show that NUMTs located close to or within ARS provide key sequence elements for replication. Thus NUMTs can act as independent origins, when inserted in an appropriate genomic context or affect the efficiency of pre-existing origins. These findings show that migratory mitochondrial DNAs can impact on the replication of the nuclear region they are inserted in

Topics: Research Article
Publisher: Public Library of Science
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Provided by: PubMed Central

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  1. (2005). A genomic view of eukaryotic DNA replication.
  2. (2011). A Mec1- and Rad53-dependent checkpoint controls late-firing origins of DNA replication.
  3. (1989). A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae.
  4. (1992). A yeast chromosomal origin of DNA replication defined by multiple functional elements.
  5. (1999). Active role of a human genomic insert in replication of a yeast artificial chromosome.
  6. (2002). Analysis of a library of macaque nuclear mitochondrial sequences confirms macaque origin of divergent sequences from old oral polio vaccine samples.
  7. Analysis of replication profiles reveals key role of RFC-Ctf18 in yeast replication stress response.
  8. (1991). Analysis of the interactions of functional domains of a nuclear origin of replication from Saccharomyces cerevisiae.
  9. (1983). Can migratory DNA activate oncogenes?
  10. (2002). Characterization of two novel splice site mutations in human factor VII gene causing severe plasma factor VII deficiency and bleeding diathesis.
  11. (2004). Continued colonization of the human genome by mitochondrial DNA.
  12. (2003). Distance from the chromosome end determines the efficiency of double strand break repair in subtelomeres of haploid yeast.
  13. (1990). Drosophila scaffold-attached regions bind nuclear scaffolds and can function as ARS elements in both budding and fission yeasts.
  14. (1985). Effect of ARS1 mutations on chromosome stability in Saccharomyces cerevisiae.
  15. (1997). Functional equivalency and diversity of cis-acting elements among yeast replication origins.
  16. (1999). Gabriel A
  17. (2005). Generation and evolutionary fate of insertions of organelle DNA in the nuclear genomes of flowering plants.
  18. (1999). Genetic methods for characterizing the cis-acting components of yeast DNA replication origins.
  19. (2001). Genome-wide distribution of ORC and MCM proteins in S. cerevisiae: highresolution mapping of replication origins.
  20. (2006). Genome-wide hierarchy of replication origin usage in Saccharomyces cerevisiae.
  21. (2006). Genome-wide identification of replication origins in yeast by comparative genomics.
  22. Genome-wide mapping of nuclear mitochondrial DNA sequences links DNA replication origins to chromosomal double-strand break formation in Schizosaccharomyces pombe. Genome Res.
  23. (2006). Genome-wide mapping of ORC and Mcm2p binding sites on tiling arrays and identification of essential ARS consensus sequences in S.
  24. (2006). Genomic mapping of single-stranded DNA in hydroxyurea-challenged yeasts identifies origins of replication.
  25. (2001). Germ line insertion of mtDNA at the breakpoint junction of a reciprocal constitutional translocation.
  26. (1991). HeLaTG cells have mitochondrial DNA inserted into the c-myc oncogene.
  27. (1991). High-efficiency transformation of yeast by electroporation.
  28. (1979). High-frequency transformation of yeast: autonomous replication of hybrid DNA molecules.
  29. (2003). Human genetic disease caused by de novo mitochondrial-nuclear DNA transfer.
  30. (1979). Isolation and characterisation of a yeast chromosomal replicator.
  31. (1983). Localization and sequence analysis of yeast origins of DNA replication.
  32. (2003). Mfold web server for nucleic acid folding and hybridization prediction.
  33. (1999). Mitochondrial DNA repairs doublestrand breaks in yeast chromosomes.
  34. (1982). Mitochondrial Genes:
  35. (2005). Mrc1 and Tof1 promote replication fork progression and recovery independently of Rad53.
  36. (1990). Mutational analysis of the consensus sequence of a replication origin from yeast chromosome III.
  37. (2004). NUMTs in sequenced eukaryotic genomes.
  38. (2007). OriDB: a DNA replication origin database.
  39. (1970). Origin of eukaryotic cells.
  40. (2004). Prediction of Saccharomyces cerevisiae replication origins.
  41. (2008). Promiscuous DNA in the nuclear genomes of hemiascomycetous yeasts.
  42. (1982). Properties of a Saccharomyces cerevisiae mtDNA segment conferring high-frequency yeast transformation.
  43. (2006). Random AT library: autonomously replicating sequence (ARS) activity of chemically synthesized random sequences for transformation of nonconventional yeast species.
  44. (2001). Replication dynamics of the yeast genome.
  45. (1980). Replicator regions of the yeast mitochondrial DNA responsible for suppressiveness.
  46. (1998). Selected nuclear LINE elements with mitochondrial-DNA-like inserts are more plentiful and mobile in tumor than in normal tissue of mouse and rat.
  47. (1990). Sequence logos: a new way to display consensus sequences.
  48. (2002). Stable replication of papillomavirus genomes in Saccharomyces cerevisiae.
  49. (1987). Sucl+ encodes a predicted 13-kilodalton protein that is essential for cell viability and is directly involved in the division cycle of Schizosaccharomyces pombe.
  50. (1997). The ARS309 chromosomal replicator of Saccharomyces cerevisiae depends on an exceptional ARS consensus sequence.
  51. (1987). The localization of replication origins
  52. (1983). The mitochondrial genome of Saccharomyces cerevisiae contains numerous, densely spaced autonomously replicating sequences.
  53. (2008). The temporal program of chromosome replication: genomewide replication in clb5{Delta} Saccharomyces cerevisiae.
  54. (2004). Transfer of a mitochondrial DNA fragment to MCOLN1 causes an inherited case of mucolipidosis IV.
  55. (2007). Unusual origin of a nuclear pseudogene in the Italian wall lizard: intergenomic and interspecific transfer of a large section of the mitochondrial genome in the genus Podarcis (Lacertidae).
  56. (2004). WebLogo: a sequence logo generator.