Meiotic cohesin serves in sister chromatid linkage and DNA repair until its subunit Rec8 is cleaved by separase. Separase is activated when its inhibitor, securin, is polyubiquitinated by the Cdc20 regulated anaphase-promoting complex (APC(Cdc20)) and consequently degraded. Differently regulated APCs (APC(Cdh1), APC(Ama1)) have not been implicated in securin degradation at meiosis I. We show that Mnd2, a factor known to associate with APC components, prevents premature securin degradation in meiosis by APC(Ama1). mnd2Delta cells lack linear chromosome axes and exhibit precocious sister chromatid separation, but deletion of AMA1 suppresses these defects. Besides securin, Sgo1, a protein essential for protection of centromeric cohesion during anaphase I, is also destabilized in mnd2delta cells. Mnd2's disappearance prior to anaphase II may activate APC(Ama1). Human oocytes may spend many years in meiotic prophase before maturation. Inhibitors of meiotic APC variants could prevent loss of chiasmata also in these cells, thereby guarding against aberrant chromosome segregation.
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http://dx.doi.org/10.1016/j.cell.2005.01.017 | DOI Listing |
EMBO Rep
January 2025
Department of Biology, University of Konstanz, 78457, Konstanz, Germany.
To ensure the correct euploid state of embryos, it is essential that vertebrate oocytes await fertilization arrested at metaphase of meiosis II. This MII arrest is mediated by XErp1/Emi2, which inhibits the ubiquitin ligase APC/C (anaphase-promoting complex/cyclosome). Cyclin B3 in complex with Cdk1 (cyclin-dependent kinase 1) is essential to prevent an untimely arrest of vertebrate oocytes in meiosis I by targeting XErp1/Emi2 for degradation.
View Article and Find Full Text PDFJ Fungi (Basel)
December 2024
Medical Research Institute, Southwest University, Chongqing 400715, China.
is a globally distributed human fungal pathogen that can cause cryptococcal meningitis with high morbidity and mortality. In this study, we identified an anaphase-promoting complex (APC) activator, Cdh1, and examined its impact on the virulence of . Our subcellular localization analysis revealed that Cdh1 is situated in the nucleus of .
View Article and Find Full Text PDFDiscov Med
December 2024
Department of Cardiology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, 330006 Nanchang, Jiangxi, China.
Background: Atherosclerosis, a chronic inflammatory condition characterized by the accumulation of lipid and fibrous elements in the arterial wall, is a major contributor to cardiovascular disease. This study aimed to investigate the regulation of apoptosis and cellular aging in human umbilical vein endothelial cells by Thousand and One Amino Acid Kinase 1 (TAOK1) via Cell division cycle 20 () in the context of atherosclerosis.
Methods: The study evaluated the impact of TAOK1 on Oxidized low-density lipoprotein (ox-LDL)-induced changes in cell viability, angiogenesis, cell senescence, apoptosis, cell cycle arrest, and related signaling pathways in human umbilical vein endothelial cells (HUVECs) using Cell Counting Kit-8, β-galactosidase staining, flow cytometry, and western blot.
Biochem Pharmacol
December 2024
Department of Molecular, Cellular, and Biomedical Sciences, Sophie Davis School of Biomedical Education, City University of New York School of Medicine, New York, NY, USA; Graduate Program in Biology, City University of New York Graduate Center, New York 10091, USA.
One possible reason for failure in achieving optimal glycemic control in patients with type 2 diabetes (T2D) is that less attention has been paid to the brain, a fundamental player in glucose homeostasis, that consumes about 25% of total glucose utilization. In addition, animal and human studies indicate that nitric oxide (NO) is a critical player in glucose metabolism. NO synthesis from L-arginine is lower in patients with T2D, and endothelial NO synthase (eNOS)-derived NO bioavailability is lower in T2D.
View Article and Find Full Text PDFbioRxiv
December 2024
The Jackson Laboratory, Bar Harbor, ME 04609.
The kinesin family member 18A () is an essential regulator of microtubule dynamics and chromosome alignment during mitosis. Functional dependency on KIF18A varies by cell type and genetic context but the heritable factors that influence this dependency remain unknown. To address this, we took advantage of the variable penetrance observed in different mouse strain backgrounds to screen for loci that modulate germ cell depletion in the absence of KIF18A.
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