SWAP, SWITCH, and STABILIZE: Mechanisms of Kinetochore–Microtubule Error Correction

Tanaka, Tomoyuki; Zhang, Tongli

doi:10.3390/cells11091462

Cited by 9 publications

(15 citation statements)

References 117 publications

(186 reference statements)

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“…Alternatively, even slightly different dynamics of two MTs in syntelic attachment would generate a twisting force on sister kinetochores. Such twisting force may facilitate the disruption of one of the two end-on attachments in syntelic attachment, thus resolving the aberrant attachment [ 69 ]. Once this happens, the twisting force would be relieved, and the other end-on attachment would not be lost.…”

Section: Kinetochore–microtubule Interactions Exchange During Error C...mentioning

confidence: 99%

Kinetochore–microtubule error correction for biorientation: lessons from yeast

Li,

Kasciukovic,

Tanaka

2024

Biochemical Society Transactions

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Accurate chromosome segregation in mitosis relies on sister kinetochores forming stable attachments to microtubules (MTs) extending from opposite spindle poles and establishing biorientation. To achieve this, erroneous kinetochore–MT interactions must be resolved through a process called error correction, which dissolves improper kinetochore–MT attachment and allows new interactions until biorientation is achieved. The Aurora B kinase plays key roles in driving error correction by phosphorylating Dam1 and Ndc80 complexes, while Mps1 kinase, Stu2 MT polymerase and phosphatases also regulate this process. Once biorientation is formed, tension is applied to kinetochore–MT interaction, stabilizing it. In this review article, we discuss the mechanisms of kinetochore–MT interaction, error correction and biorientation. We focus mainly on recent insights from budding yeast, where the attachment of a single MT to a single kinetochore during biorientation simplifies the analysis of error correction mechanisms.

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Section: Kinetochore–microtubule Interactions Exchange During Error C...mentioning

confidence: 99%

Kinetochore–microtubule error correction for biorientation: lessons from yeast

Li,

Kasciukovic,

Tanaka

2024

Biochemical Society Transactions

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“…To explain how Aurora B stops disrupting kinetochore–MT interaction when tension is applied, several models have been proposed [4, 20]. In the current study, we focus on the following two models: First, when tension is applied, the long coiled-coil region of the Ndc80C is stretched and exceeds INCENP in length, which would spatially separate Aurora B from its outer kinetochore substrates whose phosphorylation is crucial for error correction [3, 5, 21, 22] (Figure 1A, bottom).…”

Section: Introductionmentioning

confidence: 99%

“…To establish biorientation, any aberrant kinetochore-MT interactions (e.g. syntelic attachment where both sister kinetochores interact with MTs from the same spindle pole) must be weakened and disrupted in the process called error correction [1][2][3][4]. This process relies on the phosphorylation of outer kinetochore components by Aurora B kinase (Ipl1 in budding yeast) [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

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Chromosome biorientation requires Aurora B’s spatial separation from its outer kinetochore substrates but not its turnover at kinetochores

García-Rodríguez

Tanaka

2023

Preprint

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For correct chromosome segregation in mitosis, sister kinetochores must interact with microtubules from opposite spindle poles (biorientation). For this, aberrant kinetochore-microtubule interaction must be resolved (error correction) by Aurora B kinase. Once biorientation is formed, tension is applied across sister kinetochores, stabilizing kinetochore-microtubule interactions. The mechanism for this tension-dependent process has been debated. Here we study how localizations of Aurora B at different kinetochore sites affect the establishment and maintenance of biorientation in budding yeast. In the absence of the physiological Aurora B-INCENP recruitment mechanisms, engineered recruitment of Aurora B-INCENP to the inner kinetochore (Mif2) prior to biorientation supports the subsequent establishment of biorientation. By contrast, an engineered Aurora B-INCENP recruitment to the outer kinetochore (Ndc80) fails to support biorientation establishment. Furthermore, when the physiological Aurora B-INCENP recruitment mechanisms are present, an engineered Aurora B-INCENP recruitment to Mif2 during metaphase (after biorientation establishment) does not affect biorientation maintenance. By contrast, an engineered Aurora B-INCENP recruitment to Ndc80 during metaphase leads to disruption of biorientation, which is dependent on the kinase activity of Aurora B. Taken together, our results suggest that spatial separation of Aurora B from its outer kinetochore substrates is required to stabilize kinetochore-microtubule interaction when biorientation is formed and tension is applied on this interaction. Meanwhile, Aurora B shows dynamic turnover (or exchange) on the centromere and kinetochore during early mitosis. It has been thought that this turnover is crucial for error correction and biorientation, as it may help Aurora B reach its substrates in distance and/or may facilitate the Aurora B activation on the mitotic spindle. However, using the engineered Aurora B-INCENP recruitment to the inner kinetochore, we demonstrate that, even without such a turnover, Aurora B-INCENP can efficiently support biorientation. Altogether, our study provides important insights into how Aurora B promotes error correction and biorientation in a tension-dependent manner.

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“…First, the spindle assembly checkpoint (SAC) proteins accumulate on unattached kinetochores after nuclear envelope breakdown (NEBD) to monitor kinetochore-microtubule attachment state during chromosome congression 8 and delay anaphase onset until all chromosomes are properly attached to microtubules from opposing spindle poles 9 . In addition, error correction mechanisms sense and correct abnormal kinetochore-microtubule attachments 10 . However, in contrast to these plus-end monitoring processes, whether and how k-fiber minus-end focusing is monitored remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

NuMA deficiency causes micronuclei via checkpoint-insensitive k-fiber minus-end detachment from mitotic spindle poles

Toorn¹,

Gooch²,

Boerner³

et al. 2022

Preprint

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Micronuclei resulting from improper chromosome segregation foster chromosomal instability in somatic cell division cycles. To prevent micronuclei formation, bundled kinetochore-microtubules called k-fibers must be properly connected to all sister kinetochores on chromosomes via their plus-ends, whereas k-fiber minus-ends must be clustered at the two opposing spindle poles throughout mitosis. The bipolar attachment between sister kinetochores and k-fiber plus-ends is carefully monitored by the spindle assembly checkpoint and further promoted by error-correction mechanisms. However, how k-fiber minus-end clustering is maintained and monitored remains poorly understood. Here, we show that degradation of the Nuclear Mitotic Apparatus (NuMA) protein by auxin-inducible degron technologies in human cells results in micronuclei formation through k-fiber minus-end detachment from focused spindle poles during metaphase. Importantly, this k-fiber minus-end detachment creates misaligned chromosomes that maintain chromosome biorientation and do not activate the mitotic checkpoint, resulting in lagging chromosomes in anaphase. Moreover, we find that NuMA depletion causes centrosome clustering defects in tetraploid cells, leading to an increased frequency of multipolar divisions. Together, our data indicate that NuMA-mediated minus-end clustering of k-fibers and spindle microtubules is critical for faithful chromosome segregation. Similar to erroneous merotelic kinetochore attachments, detachment of k-fiber minus-ends from metaphase spindle poles evades spindle checkpoint surveillance and may therefore be a source of genomic instability in dividing cells.

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SWAP, SWITCH, and STABILIZE: Mechanisms of Kinetochore–Microtubule Error Correction

Cited by 9 publications

References 117 publications

Kinetochore–microtubule error correction for biorientation: lessons from yeast

Kinetochore–microtubule error correction for biorientation: lessons from yeast

Chromosome biorientation requires Aurora B’s spatial separation from its outer kinetochore substrates but not its turnover at kinetochores

NuMA deficiency causes micronuclei via checkpoint-insensitive k-fiber minus-end detachment from mitotic spindle poles

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