Mammalian SGO2 appears at the inner centromere domain and redistributes depending on tension across centromeres during meiosis II and mitosis

Gómez, Rocío; Valdeolmillos, Ana; Parra, María Teresa; Viera, Alberto; Carreiro, Candelas; Roncal, Fernando; Rufas, Julio S.; Barbero, José Luís; Suja, José Á.

doi:10.1038/sj.embor.7400877

Cited by 88 publications

(156 citation statements)

References 21 publications

(42 reference statements)

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“…Such a process could underlie situations in which PP2A activity is responsive to spindle tension. For example, at the second division of meiosis, bipolar pulling forces that arise between the centromere regions of separating chromosomes after anaphase onset are known to cause a centromere-localized molecule (Shugoshin) that binds the B subunit of PP2A to move away from the relevant PP2A substrate, cohesin (8,52,53). It thus has been proposed that these oppositely directed movements eliminate PP2A activity by spatially separating the enzyme from its substrate.…”

Section: Discussionmentioning

confidence: 99%

PR65, the HEAT-repeat scaffold of phosphatase PP2A, is an elastic connector that links force and catalysis

Grinthal¹,

Adamovic

Weiner³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

119

114

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PR65 is the two-layered (α-α solenoid) HEAT-repeat (Huntingtin, elongation factor 3, a subunit of protein phosphatase 2A, PI3 kinase target of rapamycin 1) scaffold of protein phosphatase PP2A. Molecular dynamics simulations predict that, at forces expected in living systems, PR65 undergoes (visco-)elastic deformations in response to pulling/pushing on its ends. At lower forces, smooth global flexural and torsional changes occur via even redistribution of stress along the hydrophobic core of the molecule. At intermediate forces, helix-helix separation along one layer ("fracturing") leads to global relaxation plus loss of contact in the other layer to unstack the affected units. Fracture sites are determined by unusual sequences in contiguous interhelix turns. Normal mode analysis of the heterotrimeric PP2A enzyme reveals that its ambient conformational fluctuations are dominated by elastic deformations of PR65, which introduce a mechanical linkage between the separately bound regulatory and catalytic subunits. PR65-dominated fluctuations of PP2A have the effect of opening and closing the enzyme's substrate binding/catalysis interface, as well as altering the positions of certain catalytic residues. These results suggest that substrate binding/catalysis are sensitive to mechanical force. Force could be imposed from the outside (e.g., in PP2A's response to spindle tension) or arise spontaneously (e.g., in PP2A's interaction with unstructured proteins such as Tau, a microtubule-associated Alzheimer's-implicated protein). The presented example supports the view that conformation and function of protein complexes can be modulated by mechanical energy inputs, as well as by chemical energy inputs from ligand binding. Given that helical-repeat proteins are involved in many cellular processes, the findings also encourage the view that mechanical forces may be of widespread importance.helical-repeat protein | protein elasticity | protein mechanotransduction | spindle tension

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Section: Discussionmentioning

confidence: 99%

PR65, the HEAT-repeat scaffold of phosphatase PP2A, is an elastic connector that links force and catalysis

Grinthal¹,

Adamovic

Weiner³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

119

114

View full text Add to dashboard Cite

show abstract

“…However, high levels of cohesin present at mammalian centromeres have been observed by microscopy (McGuinness et al 2005;Gomez et al 2007). Cohesin at the centromere may help resist the force of microtubules until all of the chromosomes are properly aligned, and this resistance may also assist in biorientation of sister chromatids.…”

Section: Subnuclear Populations Of Cohesinmentioning

confidence: 99%

“…The chromosomal sites at which cohesin associates with DNA have been mapped by ChIP-chip (chromatin immunoprecipitation followed by hybridization to DNA microarrays) in yeast, flies, and humans (Glynn et al 2004; Lengronne et al 2004;Misulovin et al 2008;Parelho et al 2008;Stedman 2008;Wendt et al 2008) and by in-situ chromosome staining (McGuinness et al 2005;Gomez et al 2007). These studies revealed both similarities as well as disparities in the localization of cohesin proteins among different eukaryotes.…”

Section: Introductionmentioning

confidence: 99%

Intersection of ChIP and FLIP, genomic methods to study the dynamics of the cohesin proteins

McNairn

Gerton

2009

Chromosome Res

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The evolutionarily conserved cohesin proteins Smc1, Smc3, Rad21 (Mcd1), and Scc3 function in the cohesin complex that provides the basis for chromosome cohesion and is involved in gene regulation. Understanding how these proteins link together the genome requires the use of wholegenome approaches to study the molecular mechanisms of these essential proteins. While chromatin immunoprecipitation followed by DNA microarray (ChIP-chip) studies have provided a snapshot in time of where these proteins associate with various genomes, the cohesin proteins are dynamic in their localization and interactions on chromatin. Study of the dynamic nature of these proteins requires approaches such as live cell imaging. We present evidence from fluorescence loss in photobleaching (FLIP) experiments in budding yeast that the decay constant of each cohesin subunit is ∼60-90 s in interphase. The decay constant on chromatin increases from G 1 to S phase to metaphase, consistent with the interaction with chromatin becoming more stable once chromosomes are cohered. A small population of Smc3 at a position consistent with centromeric location has a longer decay constant than bulk Smc3. The characterization of the interaction of cohesin with chromatin, in terms of both its position and its dynamics, may be key to understanding how this protein complex contributes to chromosome segregation and gene regulation.

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“…Sgo2 localizes at the inner centromere of mammalian chromosomes and its local distribution changes as chromosomes become bi-oriented and develop tension across the centromere. 67,68 Studies in fission yeast have also shown that Sgo2 interacts with and promotes the centromeric localization of INCENP/ Survivin. 69,70 It is less clear if the centromeric localization of Aurora kinase is also regulated by Sgo2, although it could do so indirectly via INCENP.…”

Section: How Does Aurora B Detect Kinetochore-microtubule Mis-attachmmentioning

confidence: 99%

Detection and Correction of Merotelic Kinetochore Orientation by Aurora B and its Partners

Cimini

2007

Cell Cycle

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Merotelic kinetochore orientation is a kinetochore-microtubule mis-attachment in which a single kinetochore binds microtubules to both spindle poles, rather than just one. Merotelic attachments occur frequently in early mitosis and can induce anaphase lagging chromosomes and aneuploidy if not corrected before anaphase onset. Merotelic kinetochore orientation does not interfere with chromosome alignment at the metaphase plate and does not activate the mitotic spindle checkpoint. However, a correction mechanism for merotelic attachment reduces the number of merotelic kinetochores entering anaphase, thus preventing chromosome mis-segregation. Results from many different studies support the idea that Aurora B kinase plays a critical role in this merotelic correction mechanism by phosphorylating key substrates at the kinetochore and promoting turnover of kinetochore microtubules. In addition, recent studies are starting to identify the possible 'sensors' of the system that would be able to detect the mis-attachment and communicate this to Aurora B. Here, I review these studies and discuss a model for how merotelic kinetochore orientation could be detected and corrected before anaphase onset.

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Mammalian SGO2 appears at the inner centromere domain and redistributes depending on tension across centromeres during meiosis II and mitosis

Cited by 88 publications

References 21 publications

PR65, the HEAT-repeat scaffold of phosphatase PP2A, is an elastic connector that links force and catalysis

PR65, the HEAT-repeat scaffold of phosphatase PP2A, is an elastic connector that links force and catalysis

Intersection of ChIP and FLIP, genomic methods to study the dynamics of the cohesin proteins

Detection and Correction of Merotelic Kinetochore Orientation by Aurora B and its Partners

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