Separase

from Wikipedia, the free encyclopedia

Separase , also called Separin, is a cysteine ​​protease and plays a crucial role in the regulation of mitotic and meiotic processes.

Separase passes anaphase by the hydrolysis of cohesin , a protein which is responsible for the binding of sister chromatids during the early anaphase, a. In humans, the protein separase is encoded by the gene ESPL1 (Extra Spindle Pole Bodies Like 1). The firm binding of the sister chromatids before the anaphase , as well as their timely separation during the anaphase, are crucial for cell division and proper inheritance. In mammals , sister chromatid separation occurs in two steps according to a clear mechanism. In the first step, the phosphorylation of STAG1 and STAG2 takes place in the cohesin complex, then in the second step the cohesin subunit SCC1 (RAD21) is cleaved by the separase, which initiates the final separation of the sister chromatids. In S. cerevisiae (yeast) the separase is also encoded by the gene ESPL1 and regulated by the securin Pds1. The two sister chromatids are initially connected by the Cohesin complex until the anaphase is initiated. At this point in the cell cycle , the sister chromatids are pulled apart by the mitotic spindle, so that each daughter cell that is formed ultimately contains one of the sister chromatids. If a cell is not in the dividing phase, separase is prevented from splitting cohesin through its association with another protein, securin. Likewise, the phosphorylation of the separase by the cyclin-CDK complex prevents undesired or unscheduled cleavage of the cohesin. This prevents cohesin from being split and the sister chromatids from separating prematurely in two different ways. It should be noted that separase is not effective in most organisms until a separase-securin complex is initially formed. This is because Securin helps in folding the functional conformation of the enzyme separase. In yeast, however, the formation of this complex does not seem to be necessary for the functional conformation of the separase, since the anaphase is initiated and passed through even without the presence of securin (securin deletion). The second important function of the separase is the separation of the centrioles during the anaphase. This separation allows the centrosomes to double in the next cell cycle.

Individual evidence

  1. ↑ Frank Uhlmann: Secured cutting: controlling separase at the metaphase to anaphase transition . In: EMBO reports . tape 2 , no. 6 , June 1, 2001, ISSN  1469-221X , p. 487-492 , doi : 10.1093 / embo-reports / kve113 , PMID 11415980 ( embopress.org [accessed February 8, 2018]).
  2. ↑ Hector Viadiu, Olaf Stemmann, Marc W. Kirschner, Thomas Walz: Domain structure of separase and its binding to securin as determined by EM . In: Nature Structural & Molecular Biology . tape 12 , no. 6 , June 2005, ISSN  1545-9993 , p. 552-553 , doi : 10.1038 / nsmb935 , PMID 15880121 .
  3. ↑ Ingo H. Gorr, Dominik Boos, Olaf Stemmann: Mutual Inhibition of Separase and Cdk1 by Two-Step Complex Formation . In: Molecular Cell . tape 19 , no. 1 , p. 135–141 , doi : 10.1016 / j.molcel.2005.05.022 ( elsevier.com [accessed February 8, 2018]).
  4. ↑ Nadine CD Hornig, Philip P. Knowles, Neil Q. McDonald, Frank Uhlmann: The dual mechanism of separase regulation by securin . In: Current biology: CB . tape 12 , no. 12 , June 25, 2002, ISSN  0960-9822 , p. 973-982 , PMID 12123570 .
  5. ↑ Meng-Fu Bryan Tsou, Won-Jing Wang, Kelly A. George, Kunihiro Uryu, Tim Stearns: Polo Kinase and Separase Regulate the Mitotic Licensing of Centriole Duplication in Human Cells . In: Developmental Cell . tape 17 , no. 3 , p. 344–354 , doi : 10.1016 / j.devcel.2009.07.015 ( elsevier.com [accessed February 8, 2018]).