Tension sensors reveal how the kinetochore shares its load

Salmon, Edward D.; Bloom, Kerry

doi:10.1002/bies.201600216

Cited by 25 publications

(24 citation statements)

References 97 publications

(177 reference statements)

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“…In particular, it is unclear which kinetochore functions are most important for error correction and proper chromosome segregation [28,29]. Error correction is affected by kinetochore geometry [26,[30][31][32][33] and attachment/tension sensing [21,29,34,35], although the relative contribution of different effects is not established [36][37][38][39]. Destabilization of incorrect attachments by Aurora B kinase appears to be particularly important for high-fidelity chromosome segregation [40][41][42][43].…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of chromosome biorientation and bipolar spindle assembly analyzed by computational modeling

Edelmaier

Lamson

Gergely

et al. 2020

eLife

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The essential functions required for mitotic spindle assembly and chromosome biorientation and segregation are not fully understood, despite extensive study. To illuminate the combinations of ingredients most important to align and segregate chromosomes and simultaneously assemble a bipolar spindle, we developed a computational model of fission-yeast mitosis. Robust chromosome biorientation requires progressive restriction of attachment geometry, destabilization of misaligned attachments, and attachment force dependence. Large spindle length fluctuations can occur when the kinetochore-microtubule attachment lifetime is long. The primary spindle force generators are kinesin-5 motors and crosslinkers in early mitosis, while interkinetochore stretch becomes important after biorientation. The same mechanisms that contribute to persistent biorientation lead to segregation of chromosomes to the poles after anaphase onset. This model therefore provides a framework to interrogate key requirements for robust chromosome biorientation, spindle length regulation, and force generation in the spindle.

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Section: Introductionmentioning

confidence: 99%

Mechanisms of chromosome biorientation and bipolar spindle assembly analyzed by computational modeling

Edelmaier

Lamson

Gergely

et al. 2020

eLife

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“…For the faithful segregation of mitotic chromosomes, the spindle assembly checkpoint is regulated by pushing and pulling forces generated during mitosis. When a critical tension is reached, anaphase proceeds [8]. In this review we focus primarily on mechanical transactions that occur upon the chromatin fiber in the interphase stage of the cell cycle.…”

Section: Mechanical Signal Transduction Into the Nucleusmentioning

confidence: 99%

“…At the nanoscale, macromolecular structures rely on elasticity, viscosity, and thermal motion for mechanical force development [3,4]. For example, chromosome movement during mitosis is dictated by frictional resistance [5][6][7][8]. These characteristics arise when the Reynolds number, which quantifies the relative importance of friction and inertia, is very low [9].…”

Section: Introductionmentioning

confidence: 99%

Job Opening for Nucleosome Mechanic: Flexibility Required

Pitman

Melters

Dalal

2020

Cells

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The nucleus has been studied for well over 100 years, and chromatin has been the intense focus of experiments for decades. In this review, we focus on an understudied aspect of chromatin biology, namely the chromatin fiber polymer’s mechanical properties. In recent years, innovative work deploying interdisciplinary approaches including computational modeling, in vitro manipulations of purified and native chromatin have resulted in deep mechanistic insights into how the mechanics of chromatin might contribute to its function. The picture that emerges is one of a nucleus that is shaped as much by external forces pressing down upon it, as internal forces pushing outwards from the chromatin. These properties may have evolved to afford the cell a dynamic and reversible force-induced communication highway which allows rapid coordination between external cues and internal genomic function.

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“…Alternatively, centromere-proximal attachments could simply be better at establishing tension across the bivalent at metaphase I. Tension is important for stabilizing kinetochore attachments necessary for establishing bipolar orientation (Salmon and Bloom 2017). In many systems, when tension is not present at kinetochores because of insufficient microtubule attachment, a metaphase arrest is triggered (Nicklas et al 2001).…”

Section: What Determines Conjunction In Male Meiosis?mentioning

confidence: 99%

Sex Chromosome Pairing Mediated by Euchromatic Homology inDrosophilaMale Meiosis

2020

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Diploid germline cells must undergo two consecutive meiotic divisions before differentiating as haploid sex cells. During meiosis I, homologs pair and remain conjoined until segregation at anaphase. Drosophila melanogaster spermatocytes are unique in that the canonical events of meiosis I including synaptonemal complex formation, double-strand DNA breaks, and chiasmata are absent. Sex chromosomes pair at intergenic spacer sequences within the ribosomal DNA (rDNA). Autosomes pair at numerous euchromatic homologies, but not at heterochromatin, suggesting that pairing may be limited to specific sequences. However, previous work generated from genetic segregation assays or observations of late prophase I/prometaphase I chromosome associations fail to differentiate pairing from maintenance of pairing (conjunction). Here, we separately examined the capability of X euchromatin to pair and conjoin using an rDNA-deficient X and a series of Dp(1;Y) chromosomes. Genetic assays showed that duplicated X euchromatin can substitute for endogenous rDNA pairing sites. Segregation was not proportional to homology length, and pairing could be mapped to nonoverlapping sequences within a single Dp(1;Y). Using fluorescence in situ hybridization to early prophase I spermatocytes, we showed that pairing occurred with high fidelity at all homologies tested. Pairing was unaffected by the presence of X rDNA, nor could it be explained by rDNA magnification. By comparing genetic and cytological data, we determined that centromere proximal pairings were best at segregation. Segregation was dependent on the conjunction protein Stromalin in Meiosis, while the autosomal-specific Teflon was dispensable. Overall, our results suggest that pairing may occur at all homologies, but there may be sequence or positional requirements for conjunction.

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Tension sensors reveal how the kinetochore shares its load

Cited by 25 publications

References 97 publications

Mechanisms of chromosome biorientation and bipolar spindle assembly analyzed by computational modeling

Mechanisms of chromosome biorientation and bipolar spindle assembly analyzed by computational modeling

Job Opening for Nucleosome Mechanic: Flexibility Required

Sex Chromosome Pairing Mediated by Euchromatic Homology inDrosophilaMale Meiosis

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