{"id":"doi:10.1016/j.cell.2019.06.006","kind":"article","title":"Human Artificial Chromosomes that Bypass Centromeric DNA","authors":["Logsdon GA","Gambogi CW","Liskovykh MA","Barrey EJ","Larionov V","Miga KH","Heun P","Black BE"],"author_count":8,"year":2019,"published":"2019-07-01","venue":"Cell","cited_by":87,"doi":"10.1016/j.cell.2019.06.006","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.cell.2019.06.006","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.cell.2019.06.006","updated":null,"pmid":"31348889","pmcid":"PMC6657561","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC6657561/pdf","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_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Human Artificial Chromosomes that Bypass Centromeric DNA\" by Logsdon GA, Gambogi CW, Liskovykh MA et al., https://doi.org/10.1016/j.cell.2019.06.006, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"synthetic-biology","name":"Synthetic Biology & Genome Engineering","domain_slug":"biotech"}],"cited_in_dossiers":[]}