The unique kind of human artificial chromosome: Bypassing the requirement for repetitive centromere DNA

Centromeres are essential components of all eukaryotic chromosomes, including artificial/synthetic ones built in the laboratory. In humans, centromeres are typically located on repetitive α-satellite DNA, and these sequences are the “major ingredient” in first-generation human artificial chromosomes...

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Bibliographic Details
Published in:Experimental cell research 2020-06, Vol.391 (2), p.111978-111978, Article 111978
Main Authors: Gambogi, Craig W., Dawicki-McKenna, Jennine M., Logsdon, Glennis A., Black, Ben E.
Format: Article
Language:English
Subjects:
Animals
CENP-A
Centromere
Centromere - genetics
Chromatin
Chromosomal Proteins, Non-Histone - genetics
Chromosomal Proteins, Non-Histone - metabolism
Chromosomes, Artificial, Human
DNA, Satellite - genetics
Epigenesis, Genetic
HAC
HJURP
Humans
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Summary:Centromeres are essential components of all eukaryotic chromosomes, including artificial/synthetic ones built in the laboratory. In humans, centromeres are typically located on repetitive α-satellite DNA, and these sequences are the “major ingredient” in first-generation human artificial chromosomes (HACs). Repetitive centromeric sequences present a major challenge for the design of synthetic mammalian chromosomes because they are difficult to synthesize, assemble, and characterize. Additionally, in most eukaryotes, centromeres are defined epigenetically. Here, we review the role of the genetic and epigenetic contributions to establishing centromere identity, highlighting recent work to hijack the epigenetic machinery to initiate centromere identity on a new generation of HACs built without α-satellite DNA. We also discuss the opportunities and challenges in developing useful unique sequence-based HACs.
ISSN:0014-4827
1090-2422
DOI:10.1016/j.yexcr.2020.111978