CENP-B-mediated DNA loops regulate activity and stability of human centromeres.
AFM microscopy
CENP
DNA breaks
DNA compaction
DNA topology
centromere
chromosomes
genome stability
optical tweezers
secondary structures
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
05 05 2022
05 05 2022
Historique:
received:
29
07
2021
revised:
22
02
2022
accepted:
23
02
2022
pubmed:
24
3
2022
medline:
11
5
2022
entrez:
23
3
2022
Statut:
ppublish
Résumé
Chromosome inheritance depends on centromeres, epigenetically specified regions of chromosomes. While conventional human centromeres are known to be built of long tandem DNA repeats, much of their architecture remains unknown. Using single-molecule techniques such as AFM, nanopores, and optical tweezers, we find that human centromeric DNA exhibits complex DNA folds such as local hairpins. Upon binding to a specific sequence within centromeric regions, the DNA-binding protein CENP-B compacts centromeres by forming pronounced DNA loops between the repeats, which favor inter-chromosomal centromere compaction and clustering. This DNA-loop-mediated organization of centromeric chromatin participates in maintaining centromere position and integrity upon microtubule pulling during mitosis. Our findings emphasize the importance of DNA topology in centromeric regulation and stability.
Identifiants
pubmed: 35320753
pii: S1097-2765(22)00206-4
doi: 10.1016/j.molcel.2022.02.032
pii:
doi:
Substances chimiques
Autoantigens
0
Centromere Protein A
0
Chromatin
0
Chromosomal Proteins, Non-Histone
0
DNA
9007-49-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1751-1767.e8Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.