Alternative titles; symbols
HGNC Approved Gene Symbol: EMSY
Cytogenetic location: 11q13.5 Genomic coordinates (GRCh38) : 11:76,445,018-76,553,031 (from NCBI)
Using the N-terminal domain of BRCA2 (600185) as bait in a yeast 2-hybrid screen of a mouse embryo cDNA library, Hughes-Davies et al. (2003) cloned Emsy. They also cloned human EMSY. (The authors named the protein after the first author's sister, a breast cancer nurse, because 'SISTER' appears in the first line of the protein sequence.) The deduced 1,322-amino acid protein has a calculated molecular mass of about 160 kD. EMSY has a unique N-terminal 80-amino acid domain that is conserved between several species, including plants. Western blot analysis indicated that endogenous EMSY in the nuclear fraction of a human osteosarcoma cell line had an apparent molecular mass above 160 kD.
Hughes-Davies et al. (2003) confirmed that endogenous EMSY interacted with BRCA2 in asynchronously dividing HeLa cells. They determined that the N terminus of EMSY bound a small epitope within the BRCA2 exon 3-encoded transcriptional activation domain and specifically silenced its activation potential. EMSY also interacted with the chromatin regulators HP1-beta (604511) and BS69 in vivo. Emsy relocalized to the sites of DNA damage in irradiated mouse embryonic fibroblasts. FISH analysis indicated that the EMSY gene was amplified in 5 (18%) of 28 breast cancer cell lines and in 70 (13%) of 551 sporadic breast cancers. EMSY amplification appeared to be associated with a poor prognosis.
Using FISH, Brown et al. (2006) found EMSY amplification in 52 (18%) of 285 high-grade papillary serous carcinomas, 4 (15%) of 27 high-grade endometrioid carcinomas, 3 (8%) of 38 clear cell carcinomas, and 3 (30%) of 10 undifferentiated carcinomas. Analysis of chromosome 11q13 amplification in ovarian cancer showed that EMSY localized to the region with the highest frequency of copy number gain. A highly significant correlation between EMSY gene amplification and RNA expression was also observed (p = 0.0001), and this correlation was stronger than for other candidate genes at 11q13. Brown et al. (2006) concluded that EMSY is a key oncogene within the 11q13 amplicon in ovarian cancer.
Ekblad et al. (2005) reported the crystal structure of residues 1 through 108 of EMSY at 2.0-angstrom resolution. This N-terminal region contains the ENT domain, which forms an antiparallel homodimer, followed by motifs that bind the MYND domain of BS69 and the chromoshadow domain of HP1-beta. Biophysical and nuclear magnetic resonance analyses showed that the main complex formed by the EMSY N-terminal region and the HP1-beta chromoshadow domain consists of 1 EMSY dimer sandwiched between 2 HP1-beta chromoshadow domain dimers. The HP1-beta-binding motif of EMSY was necessary and sufficient for binding the chromoshadow domain of HP1-beta.
By FISH and radiation hybrid analysis, Hughes-Davies et al. (2003) mapped the EMSY gene to chromosome 11q13.4-q13.5, within 100 kb of the GARP gene (137207).
Brown, L. A., Irving, J., Parker, R., Kim, H., Press, J. Z., Longacre, T. A., Chia, S., Magliocco, A., Makretsov, N., Gilks, B., Pollack, J., Huntsman, D. Amplification of EMSY, a novel oncogene on 11q13, in high grade ovarian surface epithelial carcinomas. Gynec. Oncol. 100: 264-270, 2006. [PubMed: 16236351] [Full Text: https://doi.org/10.1016/j.ygyno.2005.08.026]
Ekblad, C. M. S., Chavali, G. B., Basu, B. P., Freund, S. M. V., Veprintsev, D., Hughes-Davies, L., Kouzarides, T., Doherty, A. J., Itzhaki, L. S. Binding of EMSY to HP1-beta: implications for recruitment of HP1-beta and BS69. EMBO Rep. 6: 675-680, 2005. [PubMed: 15947784] [Full Text: https://doi.org/10.1038/sj.embor.7400415]
Hughes-Davies, L., Huntsman, D., Ruas, M., Fuks, F., Bye, J., Chin, S.-F., Milner, J., Brown, L. A., Hsu, F., Gilks, B., Nielsen, T., Schulzer, M., and 18 others. EMSY links the BRCA2 pathway to sporadic breast and ovarian cancer. Cell 115: 523-535, 2003. [PubMed: 14651845] [Full Text: https://doi.org/10.1016/s0092-8674(03)00930-9]