Global S&T Development Trend Analysis Platform of Resources and Environment
Shugoshin and MAD2 regulate separase-mediated chromosome separation during mitosis, in parallel to a previously identified mechanism involving the anaphase inhibitor securin.
Separation of eukaryotic sister chromatids during the cell cycle is timed by the spindle assembly checkpoint (SAC) and ultimately triggered when separase cleaves cohesion-mediating cohesin(1-3). Silencing of the SAC during metaphase activates the ubiquitin ligase APC/C (anaphase-promoting complex, also known as the cyclosome) and results in the proteasomal destruction of the separase inhibitor securin(1). In the absence of securin, mammalian chromosomes still segregate on schedule, but it is unclear how separase is regulated under these conditions(4,5). Here we show that human shugoshin 2 (SGO2), an essential protector of meiotic cohesin with unknown functions in the soma(6,7), is turned into a separase inhibitor upon association with SAC-activated MAD2. SGO2-MAD2 can functionally replace securin and sequesters most separase in securin-knockout cells. Acute loss of securin and SGO2, but not of either protein individually, resulted in separase deregulation associated with premature cohesin cleavage and cytotoxicity. Similar to securin(8,9), SGO2 is a competitive inhibitor that uses a pseudo-substrate sequence to block the active site of separase. APC/C-dependent ubiquitylation and action of the AAA-ATPase TRIP13 in conjunction with the MAD2-specific adaptor p31(comet) liberate separase from SGO2-MAD2 in vitro. The latter mechanism facilitates a considerable degree of sister chromatid separation in securin-knockout cells that lack APC/C activity. Thus, our results identify an unexpected function of SGO2 in mitotically dividing cells and a mechanism of separase regulation that is independent of securin but still supervised by the SAC.
A quantum dot device designed to host four electrons is used to demonstrate Nagaoka ferromagnetism-a model of itinerant magnetism that has so far been limited to theoretical investigation.
Engineered, highly controllable quantum systems are promising simulators of emergent physics beyond the simulation capabilities of classical computers(1). An important problem in many-body physics is itinerant magnetism, which originates purely from long-range interactions of free electrons and whose existence in real systems has been debated for decades(2,3). Here we use a quantum simulator consisting of a four-electron-site square plaquette of quantum dots(4) to demonstrate Nagaoka ferromagnetism(5). This form of itinerant magnetism has been rigorously studied theoretically(6-9) but has remained unattainable in experiments. We load the plaquette with three electrons and demonstrate the predicted emergence of spontaneous ferromagnetic correlations through pairwise measurements of spin. We find that the ferromagnetic ground state is remarkably robust to engineered disorder in the on-site potentials and we can induce a transition to the low-spin state by changing the plaquette topology to an open chain. This demonstration of Nagaoka ferromagnetism highlights that quantum simulators can be used to study physical phenomena that have not yet been observed in any experimental system. The work also constitutes an important step towards large-scale quantum dot simulators of correlated electron systems.
