title: CKAP2 ensures chromosomal stability by maintaining the integrity of microtubule nucleation sites.
abstract: Integrity of the microtubule spindle apparatus and intact cell division checkpoints are essential to ensure the fidelity of distributing chromosomes into daughter cells. Cytoskeleton-associated protein 2, CKAP2, is a microtubule-associated protein that localizes to spindle poles and aids in microtubule stabilization, but the exact function and mechanism of action are poorly understood. In the present study, we utilized RNA interference to determine the extent to which the expression of CKAP2 plays a role in chromosome segregation. CKAP2-depleted cells showed a significant increase of multipolar mitoses and other spindle pole defects. Notably, when interrogated for microtubule nucleation capacity, CKAP2-depleted cells showed a very unusual phenotype as early as two minutes after release from mitotic block, consisting of dispersal of newly polymerized microtubule filaments through the entire chromatin region, creating a cage-like structure. Nevertheless, spindle poles were formed after one hour of mitotic release suggesting that centrosome-mediated nucleation remained dominant. Finally, we showed that suppression of CKAP2 resulted in a higher incidence of merotelic attachments, anaphase lagging, and polyploidy. Based on these results, we conclude that CKAP2 is involved in the maintenance of microtubule nucleation sites, focusing microtubule minus ends to the spindle poles in early mitosis, and is implicated in maintaining genome stability.
authors.affiliation: Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Chanelle M
authors.initials: CM
authors.lastname: Case
authors.forename: Dan L
authors.initials: DL
authors.lastname: Sackett
authors.forename: Danny
authors.initials: D
authors.lastname: Wangsa
authors.forename: Tatiana
authors.initials: T
authors.lastname: Karpova
authors.forename: James G
authors.initials: JG
authors.lastname: McNally
authors.forename: Thomas
authors.initials: T
authors.lastname: Ried
authors.forename: Jordi
authors.initials: J
authors.lastname: Camps
mesh_terms: D000705:Anaphase; D045744:Cell Line, Tumor; D043171:Chromosomal Instability; D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004171:Diploidy; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D021381:Protein Transport; D064047:Spindle Poles / Q000378:metabolism; D014404:Tubulin / Q000737:chemistry
chemical_list: C114988:CKAP2 protein, human; D003598:Cytoskeletal Proteins; D014404:Tubulin