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Mis\u2010segregation of chromosomes and resulting aneuploidy leads to genetic instability, which can jeopardize the survival of an individual or population as a whole. Abnormality with segregation of genetic contents has been associated with several medical consequences including cancer, sterility, mental retardation, spontaneous abortion, miscarriages, and other birth related defects. Separase, by irreversible cleavage of cohesin complex subunit, paves the way for metaphase\/anaphase transition during the cell cycle. Both over or reduced expression and altered level of separase have been associated with several medical consequences including cancer, as a result separase now emerges as an important oncogene and potential molecular target for medical intervenes. Recently, separase is also found to be essential in separation and duplication of centrioles. Here, I review the role of separase in mitosis, meiosis, non\u2010canonical roles of separase, separase regulation, as a regulator of centriole disengagement, nonproteolytic roles, diverse substrates, structural insights, and association of separase with cancer. At the ends, I proposed a model which showed that separase is active throughout the cell cycle and there is a mere increase in separase activity during metaphase contrary to the common believes that separase is inactive throughout cell cycle except for metaphase. J. Cell. Biochem. 118: 1283\u20131299, 2017. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcb.25835","type":"journal-article","created":{"date-parts":[[2016,12,15]],"date-time":"2016-12-15T13:40:10Z","timestamp":1481809210000},"page":"1283-1299","source":"Crossref","is-referenced-by-count":22,"title":["Separase: Function Beyond Cohesion Cleavage and an Emerging Oncogene"],"prefix":"10.1002","volume":"118","author":[{"given":"Ravinder","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of Biosciences and Bioengineering  Indian Institute of Technology Bombay, Powai Mumbai 400 076 Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,1,5]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004672"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00362-2"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200702145"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.160032"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200504107"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1515\/bchm.2001.382.5.727"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0030086"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.107.085308"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.8.12.5386"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.9.9.11524"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2009.12.045"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005996"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2454"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E08-06-0637"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00131-8"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(03)00129-1"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2013.06.043"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.16.3.529"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0730733100"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00164.2014"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81211-8"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10405"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.15.1950"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.10.24.3081"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm4062"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.250351297"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(99)00160-2"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2011.0069"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/160.2.805"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.61.2.461"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.5.2.2321"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E08-10-1049"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-014-3070-z"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2013.0460"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3087"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb01052.x"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.11.4.1401"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2006.10.061"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08136"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2004.06.052"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.4.11.2147"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.9.9.11523"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2005.05.022"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103364200"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7696(08)61349-2"},{"key":"e_1_2_6_47_1","first-page":"761","article-title":"Cohesin protein SMC1 is a centrosomal protein. 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