RESUMO
Accurate chromosome segregation in mitosis depends on kinetochores that connect centromeric chromatin to spindle microtubules. Centromeres are captured by individual microtubules via a kinetochore constitutive centromere-associated network (CCAN) during chromosome segregation. CCAN contains 16 subunits, including CENP-W and CENP-T. However, the molecular recognition and mitotic regulation of the CCAN assembly remain elusive. Here, we revealed that CENP-W binds to the histone fold domain and an uncharacterized N-terminal region of CENP-T. Aurora B phosphorylates CENP-W at threonine 60, which enhances the interaction between CENP-W and CENP-T to ensure robust metaphase chromosome alignment and accurate chromosome segregation in mitosis. These findings delineate a conserved signaling cascade that integrates protein phosphorylation with CCAN integrity for the maintenance of genomic stability.
Assuntos
Aurora Quinase B , Proteínas Cromossômicas não Histona , Segregação de Cromossomos , Mitose , Aurora Quinase B/metabolismo , Humanos , Proteínas Cromossômicas não Histona/metabolismo , Proteínas Cromossômicas não Histona/genética , Fosforilação , Células HeLa , Cinetocoros/metabolismo , Ligação Proteica , Centrômero/metabolismoRESUMO
Shugoshin-1 (Sgo1) is necessary for maintaining sister centromere cohesion and ensuring accurate chromosome segregation during mitosis. It has been reported that the localization of Sgo1 at the centromere is dependent on Bub1-mediated phosphorylation of histone H2A at T120. However, it remains uncertain whether other centromeric proteins play a role in regulating the localization and function of Sgo1 during mitosis. Here, we show that CENP-A interacts with Sgo1 and determines the localization of Sgo1 to the centromere during mitosis. Further biochemical characterization revealed that lysine and arginine residues in the C-terminal domain of Sgo1 are critical for binding CENP-A. Interestingly, the replacement of these basic amino acids with acidic amino acids perturbed the localization of Sgo1 and Aurora B to the centromere, resulting in aberrant chromosome segregation and premature chromatid separation. Taken together, these findings reveal a previously unrecognized but direct link between Sgo1 and CENP-A in centromere plasticity control and illustrate how the Sgo1-CENP-A interaction guides accurate cell division.
RESUMO
A discrete-time jump fuzzy system with two hidden Markov models (HMMs) is proposed to portray the asymmetric network characteristic of a class of nonlinear networked control systems (NCSs) with random but bounded communication delays and packets dropout. The less conservative state feedback controller and the dual-model-depend guaranteed cost controller are designed base on the model. A homotopy- based iterative algorithm solving for nonlinear matrix inequality (NMI) is developed to get the control gains. Simulation examples are carried out to show the effectiveness of the proposed approaches.
Assuntos
Lógica Fuzzy , Redes Neurais de Computação , Algoritmos , Humanos , Cadeias de Markov , Dinâmica não Linear , Reconhecimento Automatizado de Padrão , Fatores de TempoRESUMO
This study used qualitative and quantitative methods, such as OWAS (Ovako working posture analysis system) and behavior observation, to analyze musculoskeletal disorder (MSD) risk factors of power line fixing work in China. Video-based sampling was used to record and analyze the frequency and posture of on-pole activities. Those key subtasks showed ergonomics characteristics of on-pole fixing tasks. Insulator-fixing was the longest subtask (33% of total working time). Bar-installing was the second longest (26% of total working time). It was evident that bar-installing and insulator-fixing were full of hazardous risks. The action categories of the 2 subtasks were higher than of the other ones. The 2 subtasks were also time-consuming, difficult and induced MSDs. Assistant linemen faced more hazardous factors than chief linemen.