Human Artificial Chromosomes that Bypass Centromeric DNA.


Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
25 07 2019
Historique:
received: 19 10 2018
revised: 07 04 2019
accepted: 03 06 2019
entrez: 27 7 2019
pubmed: 28 7 2019
medline: 28 4 2020
Statut: ppublish

Résumé

Recent breakthroughs with synthetic budding yeast chromosomes expedite the creation of synthetic mammalian chromosomes and genomes. Mammals, unlike budding yeast, depend on the histone H3 variant, CENP-A, to epigenetically specify the location of the centromere-the locus essential for chromosome segregation. Prior human artificial chromosomes (HACs) required large arrays of centromeric α-satellite repeats harboring binding sites for the DNA sequence-specific binding protein, CENP-B. We report the development of a type of HAC that functions independently of these constraints. Formed by an initial CENP-A nucleosome seeding strategy, a construct lacking repetitive centromeric DNA formed several self-sufficient HACs that showed no uptake of genomic DNA. In contrast to traditional α-satellite HAC formation, the non-repetitive construct can form functional HACs without CENP-B or initial CENP-A nucleosome seeding, revealing distinct paths to centromere formation for different DNA sequence types. Our developments streamline the construction and characterization of HACs to facilitate mammalian synthetic genome efforts.

Identifiants

pubmed: 31348889
pii: S0092-8674(19)30634-8
doi: 10.1016/j.cell.2019.06.006
pmc: PMC6657561
pii:
doi:

Substances chimiques

Centromere Protein A 0
Centromere Protein B 0
DNA, Satellite 0
Nucleosomes 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

624-639.e19

Subventions

Organisme : Wellcome Trust
ID : 092076
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 203149
Pays : United Kingdom
Organisme : NIGMS NIH HHS
ID : R35 GM130302
Pays : United States
Organisme : Wellcome Trust
ID : 103897/Z/14
Pays : United Kingdom

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

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Auteurs

Glennis A Logsdon (GA)

Department of Biochemistry and Biophysics, Graduate Program in Biochemistry and Molecular Biophysics, and Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Craig W Gambogi (CW)

Department of Biochemistry and Biophysics, Graduate Program in Biochemistry and Molecular Biophysics, and Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Mikhail A Liskovykh (MA)

Developmental Therapeutics Branch, National Cancer Institute, Bethesda, MD 20892, USA.

Evelyne J Barrey (EJ)

Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK.

Vladimir Larionov (V)

Developmental Therapeutics Branch, National Cancer Institute, Bethesda, MD 20892, USA.

Karen H Miga (KH)

Center for Biomolecular Science and Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.

Patrick Heun (P)

Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK.

Ben E Black (BE)

Department of Biochemistry and Biophysics, Graduate Program in Biochemistry and Molecular Biophysics, and Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: blackbe@pennmedicine.upenn.edu.

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