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Using human artificial chromosomes to study centromere assembly and function

Journal

CHROMOSOMA
Volume 126, Issue 5, Pages 559-575

Publisher

SPRINGER
DOI: 10.1007/s00412-017-0633-x

Keywords

Human artificial chromosomes; Centromere; Kinetochore; CENP-A; Mitosis

Funding

  1. Wellcome Trust [073915]
  2. European Molecular Biology Organization [ALTF-453-2012]
  3. Intramural Research Program of the NIH, NCI Center for Cancer Research
  4. MEXT KAKENHI [23247030, 23114008]
  5. Kazusa DNA Research Institute Foundation
  6. Grants-in-Aid for Scientific Research [23247030, 16H01414, 16H04747] Funding Source: KAKEN

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Centromeres are the site of assembly of the kinetochore, which directs chromosome segregation during cell division. Active centromeres are characterized by the presence of nucleosomes containing CENP-A and a specific chromatin environment that resembles that of active genes. Recent work using human artificial chromosomes (HAC) sheds light on the fine balance of different histone post-translational modifications and transcription that exists at centromeres for kinetochore assembly and maintenance. Here, we review the use of HAC technology to understand centromere assembly and function. We put particular emphasis on studies using the alphoidtetO HAC, whose centromere can be specifically modified for epigenetic engineering studies.

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