Extra spindle pole bodies like 1 protein (separase) (ESPL1)

Extra spindle pole bodies like 1 protein (separase), encoded by the ESPL1 gene, is a large cysteine protease essential for triggering the final separation of sister chromatids during anaphase of both mitosis and meiosis[1][2][3][5]. It acts by cleaving the α-kleisin subunit (such as RAD21 in mitosis or REC8 in meiosis) of the cohesin complex, dissolving cohesion between chromatids to ensure accurate chromosomal segregation[1][2][3]. Separase is tightly regulated by inhibitory proteins (notably securin) as well as phosphorylation cycles coordinated with the cell cycle to prevent premature chromatid separation[3][5]. Dysregulation—commonly overexpression or loss of inhibition—leads to chromosomal instability, aneuploidy, and has been repeatedly linked to tumorigenesis and poor prognosis in diverse cancers; thus, ESPL1 is both mechanistically central to proliferation and of translational interest as a therapeutic target and biomarker[4][5]. Besides its canonical role in mitosis, separase also participates in DNA damage repair, centrosome duplication, and spindle function, reflecting a range of cell cycle-related activities[5].

Other names

SeparinESP1KIAA0165SEPACaspase-like protein ESPL1Extra spindle poles-like 1 proteinCysteine protease ESPL1Extra spindle pole bodies homolog 1Separaseseparin

Proteolytic inhibition of separase blocks cohesin cleavage, arresting cells in metaphase and preventing chromatid separation[1][2][3][5]. Failed regulation can lead to chromosomal instability, a hallmark of several cancers[4].