Dataset Information

The copy-number and varied strengths of MELT motifs in Spc105 balance the strength and responsiveness of the spindle assembly checkpoint.

ABSTRACT: During mitosis, the Spindle Assembly Checkpoint (SAC) maintains genome stability while also ensuring timely anaphase onset. To maintain genome stability, the SAC must be strong to delay anaphase even if just one chromosome is unattached, but for timely anaphase onset, it must promptly respond to silencing mechanisms. How the SAC meets these potentially antagonistic requirements is unclear. Here we show that the balance between SAC strength and responsiveness is determined by the number of 'MELT' motifs in the kinetochore protein Spc105/KNL1 and their Bub3-Bub1 binding affinities. Many strong MELT motifs per Spc105/KNL1 minimize chromosome missegregation, but too many delay anaphase onset. We demonstrate this by constructing a Spc105 variant that trades SAC responsiveness for much more accurate chromosome segregation. We propose that the necessity of balancing SAC strength and responsiveness drives the dual evolutionary trend of the amplification of MELT motif number, but degeneration of their functionally optimal amino acid sequence.

SUBMITTER: Roy B

PROVIDER: S-EPMC7292645 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

The copy-number and varied strengths of MELT motifs in Spc105 balance the strength and responsiveness of the spindle assembly checkpoint.

Roy Babhrubahan B Han Simon Jy SJ Fontan Adrienne Nicole AN Joglekar Ajit P AP

eLife 20200601

During mitosis, the Spindle Assembly Checkpoint (SAC) maintains genome stability while also ensuring timely anaphase onset. To maintain genome stability, the SAC must be strong to delay anaphase even if just one chromosome is unattached, but for timely anaphase onset, it must promptly respond to silencing mechanisms. How the SAC meets these potentially antagonistic requirements is unclear. Here we show that the balance between SAC strength and responsiveness is determined by the number of 'MELT' ...[more]

PMID: 32479259

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Project description:BackgroundGeneralized Joint hypermobility (GJH) is predominantly non-symptomatic. In fact, individuals with joint flexibility usually perform better than their non-hypermobile counterparts during physical activities. Notwithstanding, strength and balance are essential to maintain the control of the extra range of motion during activities and to prevent musculoskeletal complications. There are limited and conflicting pieces of evidence in literature regarding the association between strength and balance in children with GJH.ObjectivesThe purpose of this study was to examine differences in functional strength, dynamic balance, proprioception, and isometric strength in children with and without joint hypermobility and determine the association between strength outcomes and dynamic balance.MethodA cross-sectional study was conducted among children aged 6 to 11. Hypermobility was determined using the Beighton Score, with scores ≥6 representing hypermobility. Functional strength was assessed with the Functional Strength Measure (FSM), isometric strength was determined with a handheld dynamometer (HHD), the Y-Balance Test (YBT) was used to assess dynamic balance and the Wedges test to measure proprioception.ResultsThis study included 588 participants (age: 7.97 ± 1.3 years; height: 128±10.1 cm; mass: 27.18 ± 7.98 kg). 402 children were classified as having normal mobility and 186 as being hypermobile. Hypermobile children had better functional strength in the lower extremities than children with normal range mobility but lower reach distance in the YBT. No differences in proprioception, functional strength of the upper extremity or isometric strength in the hands were found. However, isometric lower extremity force was less in hypermobile children than children with normal range mobility. Irrespective of their joint mobility, a fair significant correlation existed between total Y-balance distance and FSM items r = 0.16-0.37, p = 0.01. Correlations between total Y-balance distance and isometric strength of knee and ankle muscles ranged between r = 0.26-0.42, p = 0.001.ConclusionHypermobile joints seem to co-occur with lower extremity isometric strength, more functional strength in the lower extremities and less reaching distance in dynamic balance. The opposing direction of the results on functional and isometric strength tests highlights the importance of the type of outcome measures used to describe the association of strength and the range of motion.

Dataset Information

The copy-number and varied strengths of MELT motifs in Spc105 balance the strength and responsiveness of the spindle assembly checkpoint.

Publications

The copy-number and varied strengths of MELT motifs in Spc105 balance the strength and responsiveness of the spindle assembly checkpoint.

Similar Datasets

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