Non-B-Form DNA Is Enriched at Centromeres

Author:

Kasinathan Sivakanthan12ORCID,Henikoff Steven23

Affiliation:

1. Medical Scientist Training Program, University of Washington School of Medicine, Seattle, WA

2. Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA

3. Howard Hughes Medical Institute, Seattle, WA

Abstract

AbstractAnimal 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-form 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 nonessential. 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. This may resolve the CENP-B paradox and provide a general basis for centromere specification.

Funder

Howard Hughes Medical Institute

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Genetics,Molecular Biology,Ecology, Evolution, Behavior and Systematics

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