Kinesin‐7 CENP‐E mediates centrosome organization and spindle assembly to regulate chromosome alignment and genome stability

Abstract

Chromosome congression and alignment are essential for cell cycle progression and genomic stability. Kinesin‐7 CENP‐E, a plus‐end‐directed kinesin motor, is required for chromosome biorientation, congression and alignment in cell division. However, it remains unclear how chromosomes are aligned and segregated in the absence of CENP‐E in mitosis. In this study, we utilize the CRISPR‐Cas9 gene editing method and high‐throughput screening to establish CENP‐E knockout cell lines and reveal that CENP‐E deletion results in defects in chromosome congression, alignment and segregation, which further promotes aneuploidy and genomic instability in mitosis. Both CENP‐E inhibition and deletion lead to the dispersion of spindle poles, the formation of the multipolar spindle and spindle disorganization, which indicates that CENP‐E is necessary for the organization and maintenance of spindle poles. In addition, CENP‐E heterozygous deletion in spleen tissues also leads to the accumulation of dividing lymphocytes and cell cycle arrest in vivo. Furthermore, CENP‐E deletion also disrupts the localization of key kinetochore proteins and triggers the activation of the spindle assembly checkpoint. In summary, our findings demonstrate that CENP‐E promotes kinetochore‐microtubule attachment and spindle pole organization to regulate chromosome alignment and spindle assembly checkpoint during cell division.