Alternative titles; symbols
HGNC Approved Gene Symbol: CDCA5
Cytogenetic location: 11q13.1 Genomic coordinates (GRCh38) : 11:65,061,093-65,084,040 (from NCBI)
By differential expression analysis for genes coexpressed with cell cycle genes (e.g., CDC2; 116940), Walker (2001) identified CDCA5.
Rankin et al. (2005) identified Xenopus Cdca5, which they called p35, by a proteomic screen for anaphase-promoting complex (APC) substrates. By searching databases for sequences similar to Xenopus p35, they identified human and mouse CDCA5. The deduced human and mouse proteins contain 252 and 264 amino acids, respectively. Both contain a KEN box for APC-dependent ubiquitination. Immunofluorescence analysis revealed a punctate nuclear distribution of CDCA5 during interphase and a diffuse distribution of CDCA5 throughout the cell during mitosis. There was no apparent concentration of CDCA5 on chromatin in mitotic cells. The level of CDCA5 dropped in synchronized HeLa cells during interphase.
Nishiyama et al. (2010) found that epitope-tagged mouse sororin accumulated on chromatin in transfected HeLa cells between early S and G2 phases and became dispersed in the cytoplasm following nuclear envelope breakdown. It was also enriched at centromeres in prometaphase and metaphase.
Rankin et al. (2005) found that overexpression of CDCA5 in Xenopus embryos caused failure to resolve and segregate sister chromatids in mitosis and increased the amount of cohesin associated with metaphase chromosomes. In cultured human and mouse cells, depletion of CDCA5 caused mitotic arrest and the complete failure of sister chromatid cohesion. Rankin et al. (2005) hypothesized that CDCA5 regulates the ability of the cohesin complex to mediate sister chromatid cohesion. They proposed calling the CDCA5 protein sororin, from the Latin word soror, meaning sister, because of its role in sister chromatid cohesion.
Using RNA interference, Nishiyama et al. (2010) found that knockdown of sororin in HeLa cells caused failure of chromosome congression, consistent with a cohesion defect prior to metaphase. Depletion of Scc1 (RAD21; 606462) or Sgo1 (SGOL1; 609168) in Xenopus oocytes reduced chromosomal sororin staining, suggesting that association of sororin with mitotic chromosomes depends upon cohesin. Geminin (GMNN; 602842), a protein that inhibits cohesin loading onto DNA, abolished association of sororin with chromatin. Inhibition of DNA replication in HeLa cells also reduced sororin levels on chromatin. Knockdown studies revealed that sororin was only required for chromosome cohesion in the presence of WAPL (610754), which functions to destabilize chromosome cohesion. Immunoprecipitation studies showed that sororin interacted with the WAPL-binding protein PDS5 (see PDS5A; 613200) and displaced WAPL from its interaction with PDS5. Nishiyama et al. (2010) concluded that sororin maintains sister chromatid cohesion by inhibiting WAPL-induced dissociation of cohesin from DNA.
Hartz (2011) mapped the CDCA5 gene to chromosome 11q13.1 based on an alignment of the CDCA5 sequence (GenBank BC011000) with the genomic sequence (GRCh37).
Boyle et al. (2015) reported a 23-year-old Caucasian man with severe intellectual disability, behavioral problems, dysmorphic features, dysphagia, gastroesophageal reflux, and skeletal abnormalities associated with a heterozygous 1.6-Mb deletion at chromosome 11q12.3-q13.1 detected by chromosome microarray analysis. The deletion contained several genes, including PPP2R5B (601644), NRXN2 (600566), and CDCA5. Boyle et al. (2015) noted that CDCA5 is part of the cohesin pathway, as are genes involved in Cornelia de Lange syndrome (see, e.g., CDLS1, 122470), which may account for some of the CDLS1 features observed in the patient.
Boyle, M. I., Jespersgaard, C., Nazaryan, L., Ravn, K., Brondum-Nielsen, K., Bisgaard, A.-M., Tumer, Z. Deletion of 11q12.3-11q13.1 in a patient with intellectual disability and childhood facial features resembling Cornelia de Lange syndrome. Gene 572: 130-134, 2015. [PubMed: 26164757] [Full Text: https://doi.org/10.1016/j.gene.2015.07.016]
Hartz, P. A. Personal Communication. Baltimore, Md. 2/11/2011.
Nishiyama, T., Ladurner, R., Schmitz, J., Kreidl, E., Schleiffer, A., Bhaskara, V., Bando, M., Shirahige, K., Hyman, A. A., Mechtler, K., Peters, J.-M. Sororin mediates sister chromatid cohesion by antagonizing Wapl. Cell 143: 737-749, 2010. [PubMed: 21111234] [Full Text: https://doi.org/10.1016/j.cell.2010.10.031]
Rankin, S., Ayad, N. G., Kirschner, M. W. Sororin, a substrate of the anaphase-promoting complex, is required for sister chromatid cohesion in vertebrates. Molec. Cell 18: 185-200, 2005. Note: Erratum: Molec. Cell 18: 609 only, 2005. [PubMed: 15837422] [Full Text: https://doi.org/10.1016/j.molcel.2005.03.017]
Walker, M. G. Drug target discovery by gene expression analysis: cell cycle genes. Curr. Cancer Drug Targets 1: 73-83, 2001. [PubMed: 12188893] [Full Text: https://doi.org/10.2174/1568009013334241]