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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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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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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DOI: https://doi.org/10.1038/22139
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