Alternative titles; symbols
HGNC Approved Gene Symbol: CDCA8
Cytogenetic location: 1p34.3 Genomic coordinates (GRCh38) : 1:37,692,516-37,709,719 (from NCBI)
CDCA8 is a component of a chromosomal passenger complex required for stability of the bipolar mitotic spindle (Gassmann et al., 2004).
By database analysis, Sampath et al. (2004) identified human CDCA8 as a homolog of Xenopus Dasra B. The deduced 280-amino acid human protein, which the authors called Dasra B, shares 42% and 23% identity with Xenopus Dasra B and Dasra A, respectively. Immunofluorescence on metaphase HeLa cells revealed Dasra B in a punctate distribution on chromosomes, coincident with Aurora B (AURKB; 604970) staining.
Using a proteomic screen to identify proteins associated with histone-depleted mitotic chromosomes, Gassmann et al. (2004) identified CDCA8, which they called borealin. The deduced 280-amino acid protein contains 2 putative nuclear localization signals. Secondary structure predictions suggested borealin forms an N-terminal domain of 6 core helices and a C-terminal domain of at least 2 strands and 3 helices. Northern and Western blot analyses showed that borealin mRNA and protein levels were significantly increased in mitosis. Immunolocalization of borealin and Aurora B in HeLa cells revealed that the proteins colocalized in a dynamic pattern throughout mitosis. Western blot analysis detected borealin at an apparent molecular mass of 31 kD in HeLa cell lysates.
By immunoprecipitation of HeLa cell lysates, Sampath et al. (2004) found that Dasra B interacted with Aurora B and survivin (BIRC5; 603352). Knockdown of Dasra B by small interfering RNA resulted in severe chromosome misalignment at metaphase and accumulation of multiple interphase nuclei. In Xenopus, Dasra B associated with survivin, Aurora B, and Incenp (604411) in a chromosomal passenger complex required for chromatin-induced microtubule stabilization and spindle formation. Microtubule nucleation through the Dasra B-containing chromosomal passenger complex was distinct from the Ran (601179)-GTP pathway of chromatin-induced microtubule nucleation.
Using in vitro binding assays, Gassmann et al. (2004) showed that recombinant human borealin interacted directly with in vitro translated INCENP and survivin, but not with Aurora B or TD60 (RCC2; 609587). Borealin also readily bound itself. Mutation analysis indicated that the N-terminal domain of borealin, but not the C-terminal domain, interacted with chromosomal passengers in vivo and could perturb their targeting to centromeres but not to the spindle midzone. Knockdown of borealin in HeLa cells by RNA interference resulted in delocalization of INCENP, survivin, Aurora B, and TD60 and delayed mitotic progression. Borealin-null cells showed kinetochore-spindle misattachments, increased number of bipolar spindles associated with ectopic asters, and disrupted chromosome partitioning at anaphase. Borealin did not increase the kinase activity of Aurora B in the presence of INCENP and survivin, but it was an Aurora B target protein.
Tsukahara et al. (2010) isolated a fission yeast cyclin B (123836) mutant defective specifically in chromosome biorientation. Accordingly, Tsukahara et al. (2010) identified Cdk1 (116940)-cyclin B-dependent phosphorylation of survivin (603352). Preventing survivin phosphorylation impaired centromere chromosomal passenger complex (CPC) targeting as well as chromosome biorientation, whereas phosphomimetic survivin suppressed the biorientation defect in the cyclin B mutant. Survivin phosphorylation promoted direct binding with shugoshin (see 609168), which Tsukahara et al. (2010) defined as a conserved centromeric adaptor of the CPC. In human cells, the phosphorylation of borealin has a comparable role. Tsukahara et al. (2010) concluded that this study resolved the conserved mechanisms of CPC targeting to centromeres, highlighting a key role of Cdk1-cyclin B in chromosome biorientation.
Gassmann et al. (2004) determined that the CDCA8 gene contains 10 exons.
By genomic sequence analysis, Gassmann et al. (2004) mapped the CDCA8 gene to chromosome 1. They identified a possible pseudogene on chromosome 7.
Gassmann, R., Carvalho, A., Henzing, A. J., Ruchaud, S., Hudson, D. F., Honda, R., Nigg, E. A., Gerloff, D. L., Earnshaw, W. C. Borealin: a novel chromosomal passenger required for stability of the bipolar mitotic spindle. J. Cell Biol. 166: 179-191, 2004. [PubMed: 15249581] [Full Text: https://doi.org/10.1083/jcb.200404001]
Sampath, S. C., Ohi, R., Leismann, O., Salic, A., Pozniakovski, A., Funabiki, H. The chromosomal passenger complex is required for chromatin-induced microtubule stabilization and spindle assembly. Cell 118: 187-202, 2004. [PubMed: 15260989] [Full Text: https://doi.org/10.1016/j.cell.2004.06.026]
Tsukahara, T., Tanno, Y., Watanabe, Y. Phosphorylation of the CPC by Cdk1 promotes chromosome bi-orientation. Nature 467: 719-723, 2010. [PubMed: 20739936] [Full Text: https://doi.org/10.1038/nature09390]