Phosphorylation of the Scc2 cohesin deposition complex subunit regulates chromosome condensation through cohesin integrity

Woodman, Julie; Hoffman, Matthew; Dzieciątkowska, Monika; Hansen, Kirk C.; Megee, Paul C.

doi:10.1091/mbc.e15-03-0165

Cited by 8 publications

(6 citation statements)

References 69 publications

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“…We identified 15 phosphorylation sites in NIPBL/Scc2 required for the association of another SMC complex, cohesin, with chromosomes. It has been reported that the Scc2 phosphorylation state regulates chromosome condensation through cohesin integrity . Therefore, there is a high possibility that the identified phosphorylation sites in NIPBL/Scc2 are involved in the control of mitotic chromosome structure, similarly to those in condensin, TopoIIα, and Kif4.…”

Section: Resultsmentioning

confidence: 99%

Identification of Mitosis-Specific Phosphorylation in Mitotic Chromosome-Associated Proteins

et al. 2016

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During mitosis, phosphorylation of chromosome-associated proteins is a key regulatory mechanism. Mass spectrometry has been successfully applied to determine the complete protein composition of mitotic chromosomes, but not to identify post-translational modifications. Here, we quantitatively compared the phosphoproteome of isolated mitotic chromosomes with that of chromosomes in nonsynchronized cells. We identified 4274 total phosphorylation sites and 350 mitosis-specific phosphorylation sites in mitotic chromosome-associated proteins. Significant mitosis-specific phosphorylation in centromere/kinetochore proteins was detected, although the chromosomal association of these proteins did not change throughout the cell cycle. This mitosis-specific phosphorylation might play a key role in regulation of mitosis. Further analysis revealed strong dependency of phosphorylation dynamics on kinase consensus patterns, thus linking the identified phosphorylation sites to known key mitotic kinases. Remarkably, chromosomal axial proteins such as non-SMC subunits of condensin, TopoIIα, and Kif4A, together with the chromosomal periphery protein Ki67 involved in the establishment of the mitotic chromosomal structure, demonstrated high phosphorylation during mitosis. These findings suggest a novel mechanism for regulation of chromosome restructuring in mitosis via protein phosphorylation. Our study generated a large quantitative database on protein phosphorylation in mitotic and nonmitotic chromosomes, thus providing insights into the dynamics of chromatin protein phosphorylation at mitosis onset.

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Section: Resultsmentioning

confidence: 99%

Identification of Mitosis-Specific Phosphorylation in Mitotic Chromosome-Associated Proteins

et al. 2016

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“…Wildtype cells shifted to an elevated temperature during mitosis exhibit rDNA hypercondensation (Shen and Skibbens, 2017a; Matos-Perdomo and Machín, 2018a), but the structural basis for this dramatic change in chromatin structure remains unknown. Cohesins play a critical role in chromosome condensation, including across the rDNA locus, such that mutation in either cohesin subunits (Mcd1/Scc1, Pds5 or Scc3) or regulators (Eco1 or Scc2) all result in severe rDNA condensation defects (Guacci et al, 1997; D’Ambrosio et al, 2008; Tong and Skibbens, 2015; Skibbens et al, 1999; Hartman et al, 2000; Woodman et al, 2015; Orgil et al, 2015). These observations formally suggest that de novo cohesin deposition during mitosis may play a critical role in hyperthermic-induced rDNA hypercondensation, in contrast to the decondensation of rDNA into ‘puffs’ that occurs upon either cohesin inactivation or dissociation (Guacci et al, 1997; Ciosk et al, 2000; Shen and Skibbens, 2017a).…”

Section: Resultsmentioning

confidence: 99%

Promotion of hyperthermic-induced rDNA hypercondensation inSaccharomyces cerevisiae

Shen

Skibbens

2019

Preprint

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Ribosome biogenesis is tightly regulated through stress-sensing pathways that impact genome stability, aging and senescence. In Saccharomyces cerevisiae, ribosomal RNAs are transcribed from rDNA located on the right arm of chromosome XII. Numerous studies reveal that rDNA decondenses into a puff-like structure during interphase and condenses into a tight loop-like structure during mitosis. Intriguingly, a novel and additional mechanism of increased mitotic rDNA compaction (termed hypercondensation) was recently discovered that occurs in response to temperature stress (hyperthermic-induced) and is rapidly reversible. Here, we report that neither changes in condensin nor cohesin binding dynamics appear to play a critical role in hyperthermic-induced rDNA hypercondensation – differentiating this architectural state from normal mitotic condensation (requiring cohesins and condensins) and the premature condensation (requiring condensins) that occurs during interphase in response to nutrient starvation. A candidate genetic approach revealed that deletion of either Hsp82 or Hsc82 (Hsp90 heat shock paralogs) result in significantly reduced hyperthermic-induced rDNA hypercondensation. Intriguingly, Hsp inhibitors do not impact rDNA hypercondensation. In combination, these findings suggest that Hsp90 either stabilizes client proteins, which are sensitive to very transient thermic challenges, or directly promotes rDNA hypercondensation during preanaphase. Our findings further reveal that the high mobility group protein Hmo1 is a negative regulator of mitotic rDNA condensation, distinct from its role in promoting premature-condensation of rDNA during interphase upon nutrient starvation.

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“…Wild-type cells shifted to an elevated temperature during mitosis exhibit rDNA hypercondensation (Shen and Skibbens 2017a; Matos-Perdomo and Machín 2018a), but the structural basis for this dramatic change in chromatin structure remains unknown. Cohesins play a critical role in chromosome condensation, including across the rDNA locus, such that mutation in genes that encode either cohesin subunits (Mcd1/Scc1, Pds5, or Scc3) or regulators (Eco1 or Scc2) all result in severe rDNA condensation defects (Guacci et al 1997;Skibbens et al 1999;Hartman et al 2000;D'Ambrosio et al 2008;Guacci and Koshland 2012;Orgil et al 2015;Tong and Skibbens 2015;Woodman et al 2015). These observations formally suggest that de novo cohesin deposition during mitosis may play a critical role in hyperthermic-induced rDNA hypercondensation, in contrast to the decondensation of rDNA into "puffs" that occurs upon either cohesin inactivation or dissociation (Guacci et al 1997;Ciosk et al 2000;Shen and Skibbens 2017a).…”

Section: Hyperthermic-induced Rdna Hypercondensation Occurs In the Abmentioning

confidence: 99%

Promotion of Hyperthermic-Induced rDNA Hypercondensation in Saccharomyces cerevisiae

Shen

Skibbens

2020

Genetics

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Ribosome biogenesis is tightly regulated through stress-sensing pathways that impact genome stability, aging and senescence. In Saccharomyces cerevisiae, ribosomal RNAs are transcribed from rDNA located on the right arm of chromosome XII. Numerous studies reveal that rDNA decondenses into a puff-like structure during interphase, and condenses into a tight loop-like structure during mitosis. Intriguingly, a novel and additional mechanism of increased mitotic rDNA compaction (termed hypercondensation) was recently discovered that occurs in response to temperature stress (hyperthermic-induced) and is rapidly reversible. Here, we report that neither changes in condensin binding or release of DNA during mitosis, nor mutation of factors that regulate cohesin binding and release, appear to play a critical role in hyperthermic-induced rDNA hypercondensation. A candidate genetic approach revealed that deletion of either HSP82 or HSC82 (Hsp90 encoding heat shock paralogs) result in significantly reduced hyperthermic-induced rDNA hypercondensation. Intriguingly, Hsp inhibitors do not impact rDNA hypercondensation. In combination, these findings suggest that Hsp90 either stabilizes client proteins, which are sensitive to very transient thermic challenges, or directly promotes rDNA hypercondensation during preanaphase. Our findings further reveal that the high mobility group protein Hmo1 is a negative regulator of mitotic rDNA condensation, distinct from its role in promoting premature condensation of rDNA during interphase upon nutrient starvation.

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Phosphorylation of the Scc2 cohesin deposition complex subunit regulates chromosome condensation through cohesin integrity

Cited by 8 publications

References 69 publications

Identification of Mitosis-Specific Phosphorylation in Mitotic Chromosome-Associated Proteins

Identification of Mitosis-Specific Phosphorylation in Mitotic Chromosome-Associated Proteins

Promotion of hyperthermic-induced rDNA hypercondensation inSaccharomyces cerevisiae

Promotion of Hyperthermic-Induced rDNA Hypercondensation in Saccharomyces cerevisiae

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