# Human Artificial Chromosomes that Bypass Centromeric DNA

Article · Logsdon GA, Gambogi CW, Liskovykh MA, Barrey EJ, Larionov V, Miga KH, Heun P, Black BE

- Archive id: doi:10.1016/j.cell.2019.06.006
- Published: 2019-07-01
- Venue: Cell
- DOI: https://doi.org/10.1016/j.cell.2019.06.006
- PMID: 31348889
- PMCID: PMC6657561
- Citations: 87
- Source URL: https://doi.org/10.1016/j.cell.2019.06.006
- PDF: https://europepmc.org/articles/PMC6657561/pdf
- Provenance: europepmc

## Abstract

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.

_Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Synthetic Biology & Genome Engineering](https://space-kitty.com/topics/synthetic-biology)

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