Tension-dependent removal of pericentromeric shugoshin is an indicator of sister chromosome biorientation

Nerusheva, Olga O.; Galander, Stefan; Fernius, Josefin; Kelly, David A.; Marston, Adèle L.

doi:10.1101/gad.240291.114

Cited by 71 publications

(120 citation statements)

References 107 publications

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“…It is possible that Shugoshin proteins participate in the detection and/or correction of attachment error. Consistently, evidence has been presented for the biorientation-dependent removal of Shugoshin from pericentromeres (Eshleman and Morgan 2014;Nerusheva et al 2014), suggesting that retaining this protein at centromeres and pericentromeres may be a crucial element that keeps the spindle assembly checkpoint at an "on" state before the establishment of biorientation. However, how Shugoshin interacts with SAC remains an open question.…”

supporting

confidence: 69%

“…Sgo1p undergoes biorientation-dependent removal from chromatin (Nerusheva et al 2014), suggesting that Sgo1p and, in particular, its interaction with chromatin is tightly linked to the status of tension. Pericentric chromatin structural changes seem to be an obligatory outcome of bipolar attachment (Haase et al 2012;Verdaasdonk et al 2012;Stephens et al 2013).…”

Section: Discussionmentioning

confidence: 99%

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Identification of Tension Sensing Motif of Histone H3 inSaccharomyces cerevisiaeand Its Regulation by Histone Modifying Enzymes

et al. 2016

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To ensure genome stability during cell division, all chromosomes must attach to spindles emanating from the opposite spindle pole bodies before segregation. The tension between sister chromatids generated by the poleward pulling force is an integral part of chromosome biorientation. In budding yeast, the residue Gly44 of histone H3 is critical for retaining the conserved Shugoshin protein Sgo1p at the pericentromeres for monitoring the tension status during mitosis. Studies carried out in this work showed that Lys42, Gly44, and Thr45 of H3 form the core of a tension sensing motif (TSM). Similar to the previously reported G44S mutant, K42A, G44A, and T45A alleles all rendered cells unable to respond to erroneous spindle attachment, a phenotype suppressed by Sgo1p overexpression. TSM functions by physically recruiting or retaining Sgo1p at pericentromeres as evidenced by chromatin immunoprecipitation and by in vitro pulldown experiments. Intriguingly, the function of TSM is likely regulated by multiple histone modifying enzymes, including the histone acetyltransferase Gcn5p, and deacetylases Rpd3p and Hos2p. Defects caused by TSM mutations can be suppressed by the expression of a catalytically inactive mutant of Gcn5p. Conversely, G44S mutant cells exhibit prominent chromatin instability phenotype in the absence of RPD3. Importantly, the gcn5 2 suppressor restores the tension sensing function in tsm 2 background in a fashion that bypasses the need of stably associating Sgo1p with chromatin. These results demonstrate that the TSM of histone H3 is a key component of a mechanism that ensures faithful segregation, and that interaction with chromatin modifying enzymes may be an important part of the mitotic quality control process.KEYWORDS histone H3; chromatin; mitosis; Shugoshin; Saccharomyces cerevisiae F AITHFUL partitioning of the genome duplicates in mitosis requires that the sister chromatids be engaged in bipolar attachment to mitotic spindle. Once all chromosomes are appropriately captured by the spindles, anaphase starts with the action of separase that cleaves the cohesin complex, thus separating the two sister chromosomes (Nasmyth 2002). Premature anaphase onset causes aneuploidy, a common trait associated with spontaneous abortion, birth defects, and cancer. Chromosome biorientation is a result of sister chromatid cohesion by the cohesin complex, stable attachment of spindles to kinetochores, and that the two sister kinetochores each attach to spindles emanating from different spindle pole bodies (Kschonsak and Haering 2015). Erroneous attachment of spindles to kinetochore activates the spindle assembly checkpoint (SAC), which prevents metaphase-to-anaphase transition so that errors can be corrected (Akera and Watanabe 2016). The two essential elements of biorientation are the spindle-kinetochore interaction and the tension between sister chromatids (Goshima and Yanagida 2000;Pinsky and Biggins 2005;Wang et al. 2014). The latter results from the physical cohesion of the sister chromatids that resi...

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supporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Identification of Tension Sensing Motif of Histone H3 inSaccharomyces cerevisiaeand Its Regulation by Histone Modifying Enzymes

et al. 2016

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“…We showed that Ipl1 kinase and Sgo1 are required to prevent SAC silencing in response to syntelic attachment induced by CIK1-CC overexpression (Jin et al 2012;Jin and Wang 2013). Because the centromere localization of Sgo1 depends on H2A phosphorylation by Bub1 kinase (Fernius and Hardwick 2007;Kawashima et al 2010;Nerusheva et al 2014), Bub1 kinase activity might be required to prevent SAC silencing in response to syntelic attachment, although this kinase activity is dispensable for SAC activation (Fernius and Hardwick 2007).…”

Section: Resultsmentioning

confidence: 99%

“…The phosphorylation of budding yeast H2A at serine 121 by Bub1 is essential for centromere localization of Sgo1, and phospho-deficient h2a-S121A mutant fails to recruit Sgo1 to centromeres (Kawashima et al 2010;Nerusheva et al 2014). Thus, we postulated that h2a-S121A mutants would show premature SAC silencing similar to bub1-DK and sgo1D mutants.…”

Section: The Phosphorylation Of H2a By Bub1 Prevents Sac Silencingmentioning

confidence: 99%

Premature Silencing of the Spindle Assembly Checkpoint Is Prevented by the Bub1-H2A-Sgo1-PP2A Axis in Saccharomyces cerevisiae

Jin¹,

Bokros²,

Wang

2017

Genetics

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The spindle assembly checkpoint (SAC) monitors mistakes in kinetochore-microtubule interaction and its activation prevents anaphase entry. The SAC remains active until all chromosomes have achieved bipolar attachment which applies tension on kinetochores. Our previous data in budding yeast Saccharomyces cerevisiae show that Ipl1/Aurora B kinase and a centromereassociated protein, Sgo1, are required to prevent SAC silencing prior to tension generation, but we believe that this regulatory network is incomplete. Bub1 kinase is one of the SAC components, and Bub1-dependent H2A phosphorylation triggers centromere recruitment of Sgo1 by H2A in yeast and human cells. Although yeast cells lacking the kinase domain of Bub1 show competent SAC activation, we found that the mutant cells fail to maintain a prolonged checkpoint arrest in the presence of tensionless attachment. Mutation of the Bub1 phosphorylation site in H2A also results in premature SAC silencing in yeast cells. Previous data indicate that Sgo1 protein binds to PP2A Rts1 , and we found that rts1D mutants exhibited premature SAC silencing as well. We further revealed that sgo1 mutants with abolished binding to H2A or PP2A Rts1 displayed premature SAC silencing. Together, our results suggest that, in budding yeast S. cerevisiae, the Bub1-H2A-Sgo1-PP2A Rts1 axis prevents SAC silencing and helps prolonged checkpoint arrest prior to tension establishment at kinetochores.

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“…PP2A Cdc55 contributes to progression through the G2/M checkpoint and prevents early mitotic exit (Queralt et al 2006;Wang and Ng 2006;Yellman and Burke 2006;Rossio and Yoshida 2011). PP2A Rts1 localizes to centromeric chromatin, where it promotes condensin loading and functions in the tension-sensing mechanism of the spindle assembly checkpoint (Chan and Amon 2009;Nerusheva et al 2014;Peplowska et al 2014;Verzijlbergen et al 2014). Further, PP2A Rts1 coordinately regulates cell cycle entry and the cell size checkpoint, in part by relieving transcriptional repression of the G1 cyclin Cln3, but the mechanism of this control is not yet fully defined (Artiles et al 2009;Zapata et al 2014).…”

mentioning

confidence: 99%

Promotion of Cell Viability and Histone Gene Expression by the Acetyltransferase Gcn5 and the Protein Phosphatase PP2A in Saccharomyces cerevisiae

et al. 2016

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Histone modifications direct chromatin-templated events in the genome and regulate access to DNA sequence information. There are multiple types of modifications, and a common feature is their dynamic nature. An essential step for understanding their regulation, therefore, lies in characterizing the enzymes responsible for adding and removing histone modifications. Starting with a dosagesuppressor screen in Saccharomyces cerevisiae, we have discovered a functional interaction between the acetyltransferase Gcn5 and the protein phosphatase 2A (PP2A) complex, two factors that regulate post-translational modifications. We find that RTS1, one of two genes encoding PP2A regulatory subunits, is a robust and specific high-copy suppressor of temperature sensitivity of gcn5D and a subset of other gcn5D phenotypes. Conversely, loss of both PP2A Rts1 and Gcn5 function in the SAGA and SLIK/SALSA complexes is lethal. RTS1 does not restore global transcriptional defects in gcn5D; however, histone gene expression is restored, suggesting that the mechanism of RTS1 rescue includes restoration of specific cell cycle transcripts. Pointing to new mechanisms of acetylation-phosphorylation cross-talk, RTS1 high-copy rescue of gcn5D growth requires two residues of H2B that are phosphorylated in human cells. These data highlight the potential significance of dynamic phosphorylation and dephosphorylation of these deeply conserved histone residues for cell viability. KEYWORDS chromatin; transcription; phosphorylation; acetylation (IOC2, PAB1, RHO2, MED6, ZDS1, PP2A B56 ) A T the foundation of nuclear DNA organization in eukaryotes is the dynamic formation, movement, and modification of nucleosomes. Acetylation and phosphorylation are two histone post-translational modifications (PTMs) catalyzed by histone acetyltransferases (HATs) and kinases and reversed by histone deacetylases (HDACs) and phosphatases that alter nucleosome structure and function. Tightly regulated acetylation and phosphorylation of specific histone residues have deeply conserved functions in eukaryotes that are critical for transcriptional regulation, replication, repair, and segregation of eukaryotic genomes (Banerjee and Chakravarti 2011;Rossetto et al. 2012;Tessarz and Kouzarides 2014).One well-conserved HAT is Gcn5, which specifically targets histones H3 and H2B as part of multiple complexes (Grant et al. 1997;Eberharter et al. 1999;Grant et al. 1999;Howe et al. 2001;Sterner et al. 2002;Pray-Grant et al. 2005). Gcn5 is a key regulator of eukaryotic gene expression and acetylates H3 at promoters of active genes (Pokholok et al. 2005;Nagy and Tora 2007;Rosaleny et al. 2007). Its role as a transcriptional activator is so fundamental that Gcn5 is essential in most eukaryotes studied. An exception of note is budding yeast, where deletion of GCN5 is tolerated, but does cause a spectrum of phenotypes, including defects in gene activation, particularly for stress-regulated genes, and altered cell cycle progression (Howe et al. 2001;Huisinga and Pugh 2004;Vernarecci ...

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Tension-dependent removal of pericentromeric shugoshin is an indicator of sister chromosome biorientation

Cited by 71 publications

References 107 publications

Identification of Tension Sensing Motif of Histone H3 inSaccharomyces cerevisiaeand Its Regulation by Histone Modifying Enzymes

Identification of Tension Sensing Motif of Histone H3 inSaccharomyces cerevisiaeand Its Regulation by Histone Modifying Enzymes

Premature Silencing of the Spindle Assembly Checkpoint Is Prevented by the Bub1-H2A-Sgo1-PP2A Axis in Saccharomyces cerevisiae

Promotion of Cell Viability and Histone Gene Expression by the Acetyltransferase Gcn5 and the Protein Phosphatase PP2A in Saccharomyces cerevisiae

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