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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, RESULTS. Meshes: Anaphase, Aurora Kinases, Base Sequence, Calcium-Binding Proteins, Cell Cycle Proteins, Centromere, Chromosomal Proteins, Non-Histone, Chromosome Segregation, DNA, DNA Topoisomerases, Type II, HeLa Cells, Humans, Mad2 Proteins, Metaphase, Models, Biological, Poly-ADP-Ribose Binding Proteins, Protein Inhibitors of Activated STAT, Protein-Serine-Threonine Kinases, RNA Interference, RNA, Small Interfering, Repressor Proteins.
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Is pIASgamma required for faithful chromosome segregation in human cells? Context: The precision of the metaphase-anaphase transition ensures stable genetic inheritance. The spindle checkpoint blocks anaphase onset until the last chromosome biorients at metaphase plate, then the bonds between sister chromatids are removed and disjoined chromatids segregate to the spindle poles. But, how sister separation is triggered is not fully understood. We identify PIASgamma as a human E3 sumo ligase required for timely and efficient sister chromatid separation. In cells lacking PIASgamma, normal metaphase plates form, but the spindle checkpoint is activated, leading to a prolonged metaphase block. Sister chromatids remain cohered even if cohesin is removed by depletion of hSgo1, because DNA catenations persist at centromeres. PIASgamma-depleted cells cannot properly localize Topoisomerase II at centromeres or in the cores of mitotic chromosomes, providing a functional link between PIASgamma and Topoisomerase II.
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PIASgamma directs Topoisomerase II to specific chromosome regions that require efficient removal of DNA catenations prior to anaphase. The lack of this activity activates the spindle checkpoint, protecting cells from non-disjunction. Because DNA catenations persist without PIASgamma in the absence of cohesin, removal of catenations and cohesin rings must be regulated in parallel. Final Decision: yes