The CENP-O complex requirement varies among different cell types

Area of Science:

• Cell Biology
• Genetics
• Developmental Biology

Background:

• Centromere protein U (CENP-U) is a component of the CENP-O complex, crucial for kinetochore function.
• While CENP-U deficiency causes mitotic defects in chicken DT40 cells, these cells remain viable.
• The role of CENP-U in a whole organism context remained unclear.

Purpose of the Study:

• To investigate the functional role of CENP-U in mammalian embryogenesis and cell viability.
• To analyze the cellular phenotypes associated with CENP-U deficiency in mice.

Main Methods:

• Generation of CENP-U-deficient mice and conditional CENP-U-deficient mouse embryonic stem (ES) cells.
• Analysis of kinetochore protein localization in CENP-U-deficient cells.
• Assessment of cell viability and mitotic behavior in CENP-U-deficient cells and embryos.

Main Results:

• CENP-U-deficient mice exhibited embryonic lethality around E7.5.
• Disruption of CENP-U in mouse ES cells led to the disappearance of the CENP-O complex from kinetochores.
• CENP-U-deficient ES cells displayed abnormal mitosis and subsequent cell death, whereas mouse embryonic fibroblasts remained viable.

Conclusions:

• CENP-U is essential for mammalian embryonic viability.
• While CENP-U deficiency causes similar mitotic defects in DT40 and mouse ES cells, the cellular outcomes differ.
• Kinetochore integrity and cellular responses to mitotic errors are cell-type specific.