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Non-B-form DNA structures mark centromeres

Sivakanthan Kasinathan, View ORCID ProfileSteven Henikoff
doi: https://doi.org/10.1101/209023
Sivakanthan Kasinathan
1Medical Scientist Training Program, University of Washington School of Medicine, Seattle, WA 98195
2Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109
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Steven Henikoff
2Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109
3Howard Hughes Medical Institute, Seattle, WA 98109
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  • ORCID record for Steven Henikoff
  • For correspondence: steveh@fhcrc.org
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Abstract

Animal and plant centromeres are embedded in repetitive “satellite” DNA, but are thought to be epigenetically specified. To define genetic characteristics of centromeres, we surveyed satellite DNA from diverse eukaryotes and identified variation in <10-bp dyad symmetries predicted to adopt non-B-form conformations. Organisms lacking centromeric dyad symmetries had binding sites for sequence-specific DNA binding proteins with DNA bending activity. For example, human and mouse centromeres are depleted for dyad symmetries, but are enriched for non-B DNA and are associated with binding sites for the conserved DNA-binding protein CENP-B, which is required for artificial centromere function but is paradoxically non-essential. We also detected dyad symmetries and predicted non-B-form DNA structures at neocentromeres, which form at ectopic loci. We propose that centromeres form at non-B-form DNA because of dyad symmetries or are strengthened by sequence-specific DNA binding proteins. Our findings resolve the CENP-B paradox and provide a general basis for centromere specification.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted October 25, 2017.
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Non-B-form DNA structures mark centromeres
Sivakanthan Kasinathan, Steven Henikoff
bioRxiv 209023; doi: https://doi.org/10.1101/209023
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Non-B-form DNA structures mark centromeres
Sivakanthan Kasinathan, Steven Henikoff
bioRxiv 209023; doi: https://doi.org/10.1101/209023

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