Graduate School of Frontier Biosciences, Osaka University


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

Journal Mol Biol Cell 26, 3768-3776 (2015)
Authors Harsh Nagpal (1, 2), Tetsuya Hori (1), Ayako Furukawa (3), Kenji Sugase (3), Akihisa Osakabe (4), Hitoshi Kurumizaka (4), and Tatsuo Fukagawa (1, 2)

  1. Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan
  2. Department of Molecular Genetics, National Institute of Genetics and Graduate University for Advanced Studies (SOKENDAI), Mishima, Shizuoka 411-8540, Japan
  3. Bioorganic Research Institute, Suntory Foundation for Life Sciences, Osaka 618-8503, Japan
  4. Graduate School of Advanced Science & Engineering, Waseda University, Shinjuku, Tokyo 162-8480, Japan
Title Dynamic changes in the CCAN organization through CENP-C during cell-cycle progression
PubMed 26354420
Laboratory Laboratory of Chromosome Biology 〈Prof. Fukagawa〉
Description Background

The key objective of mitosis is equal distribution of genetic material to the daughter cells. In eukaryotes, this process is accomplished by attachment of the duplicated sister chromatids to a bipolar mitotic spindle and their subsequent separation and segregation to the daughter cells during mitosis (Figure 1). A large protein complex, known as the kinetochore is formed at the centromeric region of each chromosome, which mediates this attachment between centromeric chromatin and spindle microtubules for faithful chromosome segregation. To understand chromosome segregation we must understand architecture of centromeres and kinetochores.

Topics of current paper

The kinetochore is a crucial structure for faithful chromosome segregation during mitosis and is formed in the centromeric region of each chromosome. The 16-subunit protein complex, known as the constitutive centromere-associated network (CCAN) forms the foundation for kinetochore assembly on the centromeric chromatin. In this study we focused on relationship of CENP-C (a component of CCAN) with other CCAN proteins and tried to clarify how CENP-C is involved in CCAN organization.

We analyzed the relationship of CENP-C with the CENP-H complex during progression of the cell cycle. We demonstrated that the middle portion of chicken CENP-C (CENP-C166–324) is sufficient for centromere localization during interphase, through association with the CENP-L-N complex. The C-terminus of CENP-C (CENP-C601–864) is essential for centromere localization during mitosis, through binding to CENP-A nucleosomes, independent of the CENP-H complex. Based on these results, we propose that CCAN organization changes dynamically during progression of the cell cycle (Figure 2).

Figure 1. Cell cycle progression and diagram of centromere.


Figure 2. Model showing cell cycle-dependent kinetochore organization. During interphase, the N-terminus of CENP-N preferentially binds to CENP-A nucleosomes, whereas the C-terminus of CENP-N and CENP-L bind to the middle portion of CENP-C. The CENP-C-CENP-A interaction is probably weak during interphase. In contrast, CENP-C binds to CENP-A nucleosomes via its C-terminal dimerization domain during mitosis. CENP-N may not associate with CENP-A nucleosomes, because CENP-N does not bind to compact chromatin.