The CENP-O complex requirement varies among different cell types.
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.
Department of Molecular Genetics, National Institute of Genetics and The Graduate University for Advanced Studies, Mishima, Shizuoka, 411-8540, Japan.
Naoko
N
Kagawa
Tetsuya
T
Hori
Yuko
Y
Hoki
Osamu
O
Hosoya
Kimiko
K
Tsutsui
Yumiko
Y
Saga
Takashi
T
Sado
Tatsuo
T
Fukagawa
D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D002645:Chickens; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D002869:Chromosome Aberrations; D047108:Embryonic Development; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D051379:Mice; D008938:Mitosis; D046912:Multiprotein Complexes / Q000378:metabolism*; D009928:Organ Specificity; D021381:Protein Transport
D002868:Chromosomal Proteins, Non-Histone; D046912:Multiprotein Complexes