Chromosome segregation in mitosis and meiosis is triggered by activation of a large protease, separase. While it has been known for some time that the anaphase inhibitor securin regulates separase activity recent work shows that this is only half the story. In vertebrates Cdk1-dependent inhibition of separase represents a second, securin-independent branch of anaphase regulation. Furthermore, an unanticipated ability of separase to inhibit Cdk1 suggests additional, nonproteolytic functions of separase.
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http://dx.doi.org/10.4161/cc.5.1.2296 | DOI Listing |
Separase plays a central role in chromosome separation during mitosis and in centrosome cycle. Tight control of separase activity is required to prevent unscheduled resolution of sister chromatid cohesion and centrosome aberrations, thereby preserving genome stability. In mammals, despite their disassembly in early mitosis, some nuclear envelope components possess mitotic roles, but links with separase activity remain unexplored.
View Article and Find Full Text PDFJ Cell Biol
February 2025
Department of Obstetrics and Gynecology, C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, MI, USA.
Separase regulates multiple aspects of the metaphase-to-anaphase transition. Separase cleaves cohesin to allow chromosome segregation and localizes to vesicles to promote exocytosis. The anaphase-promoting complex/cyclosome (APC/C) activates separase by ubiquitinating its inhibitory chaperone, securin, triggering its degradation.
View Article and Find Full Text PDFbioRxiv
November 2024
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States.
Cells coordinate diverse events at anaphase onset, including separase activation, cohesin cleavage, chromosome separation, and spindle reorganization. Regulation of the XMAP215 family member and microtubule polymerase, Stu2, at the metaphase-anaphase transition determines a specific redistribution from kinetochores to spindle microtubules. We show that cells modulate Stu2 kinetochore-microtubule localization by Polo-like kinase1/Cdc5-mediated phosphorylation of T866, near the Stu2 C-terminus, thereby promoting dissociation from the kinetochore Ndc80 complex.
View Article and Find Full Text PDFbioRxiv
October 2024
Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, University of California-San Diego, La Jolla, CA 92093.
The mutants designated (cell lysis) cause cell lysis at elevated temperatures. The mutation, previously localized to an 80 kilobase region between and on the right arm of chromosome VII, has been used for mutation mapping and in recombination assays, but its genetic identity has remained unknown. Whole genome sequencing of mutant and wild-type strains revealed four missense mutations specific to the mutant strain in the - interval, three of these missense mutations affected essential genes.
View Article and Find Full Text PDFSci Adv
October 2024
Instituto de Química Física "Blas Cabrera," CSIC (IQF-CSIC), 28006 Madrid, Spain.
How CRISPR-Cas and cyclic oligonucleotide-based antiphage signaling systems (CBASS) are coordinately deployed against invaders remains unclear. We show that a locus containing two CBASS and one type III-B CRISPR-Cas system, regulated by the transmembrane anti-σ DdvA and its cognate extracytoplasmic function (ECF) σ DdvS, can defend against a phage. Cryo-electron microscopy reveals DdvA-DdvS pairs assemble as arrow-shaped transmembrane dimers.
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