4.2 Article

The CENP-O complex requirement varies among different cell types

Journal

CHROMOSOME RESEARCH
Volume 22, Issue 3, Pages 293-303

Publisher

SPRINGER
DOI: 10.1007/s10577-014-9404-1

Keywords

Centromere; Kinetochore; CENP-O; complex proteins

Funding

  1. Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan
  2. Precursory Research for Embryonic Science and Technology of the Japan Science and Technology Agency
  3. MEXT
  4. Grants-in-Aid for Scientific Research [26440190, 25116002, 25287099, 23310133, 21115005] Funding Source: KAKEN

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CENP-U (CENP-50) is a component of the CENP-O complex, which includes CENP-O, CENP-P, CENP-Q, CENP-R, and CENP-U and is constitutively localized at kinetochores throughout the cell cycle in vertebrates. Although CENP-U deficiency results in some mitotic defects in chicken DT40 cells, CENP-U-deficient chicken DT40 cells are viable. To examine the functional roles of CENP-U in an organism-dependent context, we generated CENP-U-deficient mice. The CENP-U-deficient mice died during early embryogenesis (approximately E7.5). Thus, conditional CENP-U-deficient mouse ES cells were generated to analyze CENP-U-deficient phenotypes at the cell level. When CENP-U was disrupted in the mouse ES cells, all CENP-O complex proteins disappeared from kinetochores. In contrast, other kinetochore proteins were recruited in CENP-U-deficient mouse ES cells as CENP-U-deficient DT40 cells. However, the CENP-U-deficient ES cells died after exhibiting abnormal mitotic behavior. Although CENP-U was essential for cell viability during mouse early embryogenesis, CENP-U-deficient mouse embryonic fibroblast cells were viable, similar to the DT40 cells. Thus, although both DT40 and ES cells with CENP-U deficiency have similar mitotic defects, cellular responses to mitotic defects vary among different cell types.

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