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Dynamic changes in CCAN organization through CENP-C during cell-cycle progression.

Harsh Nagpal1, Tetsuya Hori2, Ayako Furukawa3

  • 1Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan Department of Molecular Genetics, National Institute of Genetics and Graduate University for Advanced Studies (SOKENDAI), Mishima, Shizuoka 411-8540, Japan.

Molecular Biology of the Cell
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The constitutive centromere-associated network (CCAN) organization dynamically changes during the cell cycle. Specific regions of CENP-C mediate centromere localization in interphase and mitosis, revealing cell cycle-dependent CCAN assembly.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • The kinetochore is essential for accurate chromosome segregation during cell division.
  • The constitutive centromere-associated network (CCAN) is a protein complex forming the kinetochore's foundation.
  • Understanding CCAN organization is key to comprehending kinetochore assembly and function.

Purpose of the Study:

  • To investigate the dynamic organization of CCAN proteins during the cell cycle.
  • To determine how centromeric protein C (CENP-C) interacts with other CCAN components at different cell cycle stages.

Main Methods:

  • Analysis of chicken CENP-C protein fragments.
  • Assessment of centromere localization during interphase and mitosis.
  • Investigation of interactions with CENP-A nucleosomes and the CENP-H complex.

Main Results:

  • The middle region of CENP-C (CENP-C(166-324)) mediates interphase localization, potentially via the CENP-L-N complex.
  • The C-terminus of CENP-C (CENP-C(601-864)) is crucial for mitotic localization by binding CENP-A nucleosomes, independently of the CENP-H complex.
  • These findings indicate distinct mechanisms for CENP-C localization throughout the cell cycle.

Conclusions:

  • CCAN organization is not static but changes dynamically during cell cycle progression.
  • The differential localization mechanisms of CENP-C highlight a regulated assembly process for the functional kinetochore.
  • This study provides insights into the cell cycle-dependent structural dynamics of the centromere.