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Structural insights into human CCAN complex assembled onto DNA.

Tian Tian1, Lili Chen1, Zhen Dou1,2

  • 1MOE Key Laboratory for Cellular Dynamics, the First Affiliated Hospital, CAS Center for Excellence in Biomacromolecules, and School of Life Sciences, University of Science and Technology of China, Hefei, China.

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|September 9, 2022
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Summary
This summary is machine-generated.

Human kinetochores use the constitutive centromere-associated network (CCAN) to bind DNA and ensure accurate chromosome segregation during mitosis. This interaction is crucial for kinetochore assembly and function.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Accurate chromosome segregation during mitosis relies on kinetochores connecting centromeric chromatin to spindle microtubules.
  • Budding yeast possess simple centromeres linked to microtubules via the constitutive centromere-associated network (CCAN).
  • Human centromeres are complex, involving millions of DNA base pairs and multiple microtubule attachments.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which the human CCAN interacts with duplex DNA.
  • To understand how these interactions facilitate accurate chromosome segregation in human cells.
  • To reveal the structural basis of CCAN function in kinetochore assembly.

Main Methods:

  • Cryo-electron microscopy to determine structural details.
  • Functional analyses to assess the role of DNA binding in mitosis.

Main Results:

  • The human CCAN structure reveals cooperative interactions between its sub-complexes.
  • Human CCAN topologically entraps duplex DNA.
  • CENP-N binds DNA within the CCAN complex, not the RG-loop of CENP-A.
  • DNA binding by CENP-LN is essential for centromere localization and chromosome segregation.

Conclusions:

  • The study provides molecular insights into human CCAN-DNA interactions.
  • These interactions are critical for kinetochore assembly and function during mitosis.
  • The findings clarify mechanisms underlying accurate chromosome segregation in human cells.