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Orientation of DNA replication establishes mating-type switching pattern in S. pombe

Abstract

The fission yeast Schizosaccharomyces pombe normally has haploid cells of two mating types, which differ at the chromosomal locus mat1. After two consecutive asymmetric cell divisions, only one in four ‘grand-daughter’ cells undergoes a ‘mating-type switch’, in which genetic information is transferred to mat1 from the mat2-P or mat3-M donor loci1,2,3,4. This switching pattern probably results from an imprinting event at mat1 that marks one sister chromatid in a strand-specific manner3,4,5, and is related to a site-specific, double-stranded DNA break at mat16,7. Here we show that the genetic imprint is a strand-specific, alkali-labile DNA modification at mat1. The DNA break is an artefact, created from theimprint during DNA purification. We also propose and test themodel that mat1 is preferentially replicated by a centromere-distal origin(s), so that the strand-specific imprint occurs only during lagging-strand synthesis. Altering the origin of replication, by inverting mat1 or introducing an origin of replication, affects the imprinting and switching efficiencies in predicted ways. Two-dimensional gel analysis confirmed that mat1 is preferentially replicated by a centromere-distal origin(s). Thus, the DNA replication machinery may confer different developmental potential to sister cells.

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Figure 1: Characterization of the imprint.
Figure 2: Mating-type region and the pattern of switching of mating types.
Figure 3: Analysis of rearrangements.
Figure 4: Assessment of origin activity.
Figure 5: Determination of replication orientation at mat1 of strain JZ108.

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References

  1. Miyata, H. & Miyata, M. Mode of conjugation in homothallic cells of Schizosaccharomyces pombe. J.Gen. Appl. Microbiol. 27, 365–371 (1981).

    Article  Google Scholar 

  2. Egel, R. & Eie, B. Cell lineage asymmetry in Schizosaccharomyces pombe : unilateral transmission of a high-frequency state of mating-type switching in diploid pedigrees. Curr. Genet. 12, 429–433 (1987).

    Article  Google Scholar 

  3. Klar, A. J. S. Differentiated parental DNA strands confer developmental asymmetry on daughter cells in fission yeast. Nature 326, 466–470 (1987).

    Article  ADS  CAS  Google Scholar 

  4. Klar, A. J. S. The developmental fate of fission yeast cells is determined by the pattern of inheritance of parental and grandparental DNA strands. EMBO J. 9, 1407–1415 (1990).

    Article  CAS  Google Scholar 

  5. Klar, A. J. S. & Bonaduce, M. J. The mechanism of fission yeast mating-type interconversion: evidence for two types of epigenetically inherited chromosomal imprinted events. Cold Spring Harb. Symp. Quant. Biol. 58, 457–465 (1993).

    Article  CAS  Google Scholar 

  6. Beach, D. H. Cell type switching by DNA transposition in fission yeast. Nature 305, 682–687 (1983).

    Article  ADS  CAS  Google Scholar 

  7. Nielsen, O. & Egel, R. Mapping the double-strand breaks at the mating-type locus in fission yeast by genomic sequencing. EMBO J. 8, 269–276 (1989).

    Article  CAS  Google Scholar 

  8. Klar, A. J. S. & Miglio, L. M. Initiation of meiotic recombination by double-strand DNA breaks in S.pombe. Cell 46, 725–731 (1986).

    Article  CAS  Google Scholar 

  9. Moreno, S. A., Klar, A. J. S. & Nurse, P. Molecular genetic analysis of fission yeast Schizosaccharomyces pombe. Methods Enzymol. 194, 795–823 (1991).

    Article  CAS  Google Scholar 

  10. Egel, R., Beach, D. H. & Klar, A. J. S. Genes required for initiation and resolution steps of mating-type switching in fission yeast. Proc. Natl Acad. Sci. USA 81, 3481–3485 (1984).

    Article  ADS  CAS  Google Scholar 

  11. Singh, J. & Klar, A. J. S. DNA polymerase-α is essential for mating-type switching in fission yeast. Nature 361, 271–273 (1993).

    Article  ADS  CAS  Google Scholar 

  12. Caddle, M. S. & Calos, M. P. Specific initiation at an origin of replication from Schizosaccharomyces pombe. Mol. Cell. Biol. 14, 1796–1805 (1994).

    Article  CAS  Google Scholar 

  13. Clyne, R. K. & Kelly, T. J. Genetic analysis of an ARS element from the fission yeast Schizosaccharomyces pombe. EMBO J. 14, 6348–6357 (1995).

    Article  CAS  Google Scholar 

  14. Brewer, B. J., Lockshon, D. & Fangman, W. L. The arrest of replication forks in the rDNA of yeast occurs independently of transcription. Cell 71, 267–276 (1992).

    Article  CAS  Google Scholar 

  15. Arcangioli, B. Asite- and strand-specific DNA break confers asymmetric switching potential in fission yeast. EMBO J. 17, 4503–4510 (1998).

    Article  CAS  Google Scholar 

  16. Klar, A. J. S. Lineage-dependent mating-type transposition in fission and budding yeast. Curr. Opin. Genet. Dev. 3, 745–751 (1993).

    Article  CAS  Google Scholar 

  17. Sambrook, J., Fritsch, E. F. & Maniatis, T. Molecular Cloning: A Laboratory Manual2nd ed (Cold Spring Harbor Laboratory Press, New York, (1989).

    Google Scholar 

  18. MacDonell, M. W., Simon, M. W. & Studier, F. W. Analysis of restriction fragments of T7 DNA and determination of molecular weights by electrophoresis in neutral and alkaline gels. J. Mol. Biol. 110, 119–146 (1977).

    Article  Google Scholar 

  19. Egel, R. in Molecular Biology of the Fission Yeast (eds Nasim, A., Young, P. &Johnson, B. F.) 31–74 (Academic, San Diego, (1989).

    Book  Google Scholar 

  20. Klar, A. J. S., Ivanova, A. V., Dalgaard, J. Z., Bonaduce, M. J. & Grewal, S. I. S. in Epigenetics (ed. Cardew, G.) 87–103 (Novartis Foundation Symposium 214, Wiley, Chichester, (1998).

    Google Scholar 

  21. Arcangioli, B. & Klar, A. J. S. Anovel switch-activating site (SAS1) and its cognate binding factor (SAP1) required for efficient mat1 switching in Schizosaccharomyces pombe. EMBO J. 10, 3025–3032 (1991).

    Article  CAS  Google Scholar 

  22. Styrkarsdottir, U., Egel, R. & Nielsen, O. The smt-0 mutation which abolishes mating-type switching in fission yeast is a deletion. Curr. Genet. 23, 184–186 (1993).

    Article  CAS  Google Scholar 

  23. Gerring, S. L., Connelly, C. & Hieter, P. in Guide to Yeast Genetics and Molecular Biology (eds Fink, G. &Guthrie, C.) 57–76 (Academic, San Diego, (1991).

    Book  Google Scholar 

  24. Bresch, C., Muller, G. & Egel, R. Genes involved in meiosis and sporulation of a yeast. Mol. Gen. Genet. 102, 301–306 (1968).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank our colleagues at ABL for suggestions and helpful discussions; B. Brewer, M. Hoant and S. Hunt for help with the analysis of replication intermediates; A. Arthur for editorial suggestions; and R. Frederickson for the art work. This work was sponsored by the Danish Natural Science Research Council (J.Z.D.) and the National Cancer Institute, Department of Health and Human Services, under contract with ABL. The contents of this article do not necessarily reflect the views or politics of the DHHS, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

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Correspondence to Amar J. S. Klar.

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Dalgaard, J., Klar, A. Orientation of DNA replication establishes mating-type switching pattern in S. pombe. Nature 400, 181–184 (1999). https://doi.org/10.1038/22139

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