Phosphorylation of H2A by Bub1 Prevents Chromosomal Instability Through Localizing Shugoshin

Science ◽  
2009 ◽  
Vol 327 (5962) ◽  
pp. 172-177 ◽  
Author(s):  
Shigehiro A. Kawashima ◽  
Yuya Yamagishi ◽  
Takashi Honda ◽  
Kei-ichiro Ishiguro ◽  
Yoshinori Watanabe
Keyword(s):  
Protein Kinase ◽  
Schizosaccharomyces Pombe ◽  
Fission Yeast ◽  
Chromosome Segregation ◽  
Chromosomal Instability ◽  
Histone H2a

Bub1 is a multi-task protein kinase required for proper chromosome segregation in eukaryotes. Impairment of Bub1 in humans may lead to chromosomal instability (CIN) or tumorigenesis. Yet, the primary cellular substrate of Bub1 has remained elusive. Here, we show that Bub1 phosphorylates the conserved serine 121 of histone H2A in fission yeast Schizosaccharomyces pombe. The h2a-SA mutant, in which all cellular H2A-S121 is replaced by alanine, phenocopies the bub1 kinase-dead mutant (bub1-KD) in losing the centromeric localization of shugoshin proteins. Artificial tethering of shugoshin to centromeres largely restores the h2a-SA or bub1-KD–related CIN defects, a function that is evolutionally conserved. Thus, Bub1 kinase creates a mark for shugoshin localization and the correct partitioning of chromosomes.

Cold induces stress-activated protein kinase-mediated response in the fission yeast Schizosaccharomyces pombe

2002 ◽  
Vol 269 (20) ◽  
pp. 5056-5065 ◽  
Author(s):  
Teresa Soto ◽  
Francisco F. Beltrán ◽  
Vanessa Paredes ◽  
Marisa Madrid ◽  
Jonathan B. A. Millar ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Schizosaccharomyces Pombe ◽  
Fission Yeast

Live Imaging of Chromosome Segregation during Meiosis in the Fission Yeast Schizosaccharomyces pombe

2017 ◽  
Vol 2017 (9) ◽  
pp. pdb.prot091769
Author(s):  
Akira Yamashita ◽  
Takeshi Sakuno ◽  
Yoshinori Watanabe ◽  
Masayuki Yamamoto
Keyword(s):  
Schizosaccharomyces Pombe ◽  
Fission Yeast ◽  
Chromosome Segregation ◽  
Live Imaging

scholarly journals Discrete roles of the Spc1 kinase and the Atf1 transcription factor in the UV response of Schizosaccharomyces pombe.

1997 ◽  
Vol 17 (6) ◽  
pp. 3356-3363 ◽  
Author(s):  
G Degols ◽  
P Russell
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Protein Kinase ◽  
Schizosaccharomyces Pombe ◽  
Fission Yeast ◽  
Uv Irradiation ◽  
Double Mutant ◽  
Uv Response ◽  
Rad Mutants ◽  
Mutant Cells

Exposure of mammalian cells to UV irradiation or alkylating agents leads to the activation of the c-Jun N-terminal kinase and p38 stress-activated protein kinase cascades, phosphorylation of c-Jun and ATF-2 bZIP transcription factors, and finally to selective induction of gene expression. This UV response is believed to be crucially important for cell survival, although conclusive evidence is lacking. Here, we address this issue by investigating a homologous UV response pathway in the fission yeast Schizosaccharomyces pombe. In fission yeast cells, UV irradiation induces activation of Spc1 stress-activated protein kinase, which in turn phosphorylates the Atf1 bZIP transcription factor. spc1 mutants are hypersensitive to killing by UV at a level equivalent to some checkpoint rad mutants. Whereas checkpoint rad mutants fail to arrest division in response to DNA damage, spc1 mutants are defective at resuming cell division after UV exposure. Levels of basal and UV-induced transcription of ctt1+, which encodes a catalase believed important for combating oxidative stress caused by UV, are extremely low in spc1 mutants. Atf1 is required for UV-induced transcription of ctt1+, but atf1 mutants are not hypersensitive to killing by UV. This surprising finding is explained by the observation that ctt1+ basal expression is unaffected in atf1 single mutant and spc1 atf1 double mutant cells, suggesting that unphosphorylated Atf1 represses ctt1+ expression in spc1 cells. In fact, the level of UV sensitivity of spc1 atf1 double mutant cells is intermediate between those of the wild type and spc1 mutants. These findings suggest the following. (i) Key properties of UV response mechanisms are remarkably similar in mammals and S. pombe. (ii) Activation of Spc1 kinase greatly enhances survival of UV-irradiated cells. (iii) Induction of gene expression by activation of Atf1 may not be the most important mechanism by which stress-activated kinases function in the UV response.

scholarly journals Distinct Regulatory Proteins Control the Graded Transcriptional Response to Increasing H2O2 Levels in Fission Yeast Schizosaccharomyces pombe

2002 ◽  
Vol 13 (3) ◽  
pp. 805-816 ◽  
Author(s):  
Janet Quinn ◽  
Victoria J. Findlay ◽  
Keren Dawson ◽  
Jonathan B.A. Millar ◽  
Nic Jones ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Protein Kinase ◽  
Schizosaccharomyces Pombe ◽  
Fission Yeast ◽  
Transcriptional Response ◽  
Regulatory Proteins ◽  
Mitogen Activated Protein Kinase ◽  
Two Component ◽  
Mitogen Activated Protein ◽  
Low Levels

The signaling pathways that sense adverse stimuli and communicate with the nucleus to initiate appropriate changes in gene expression are central to the cellular stress response. Herein, we have characterized the role of the Sty1 (Spc1) stress-activated mitogen-activated protein kinase pathway, and the Pap1 and Atf1 transcription factors, in regulating the response to H2O2 in the fission yeast Schizosaccharomyces pombe. We find that H2O2 activates the Sty1 pathway in a dose-dependent manner via at least two sensing mechanisms. At relatively low levels of H2O2, a two component-signaling pathway, which feeds into either of the two stress-activated mitogen-activated protein kinase kinase kinases Wak1 or Win1, regulates Sty1 phosphorylation. In contrast, at high levels of H2O2, Sty1 activation is controlled predominantly by a two-component independent mechanism and requires the function of both Wak1 and Win1. Individual transcription factors were also found to function within a limited range of H2O2 concentrations. Pap1 activates target genes primarily in response to low levels of H2O2, whereas Atf1 primarily controls the transcriptional response to high concentrations of H2O2. Our results demonstrate that S. pombe uses a combination of stress-responsive regulatory proteins to gauge and effect the appropriate transcriptional response to increasing concentrations of H2O2.

scholarly journals Kinetochore Targeting of Fission Yeast Mad and Bub Proteins Is Essential for Spindle Checkpoint Function but Not for All Chromosome Segregation Roles of Bub1p

2004 ◽  
Vol 24 (22) ◽  
pp. 9786-9801 ◽  
Author(s):  
Vincent Vanoosthuyse ◽  
Rebekka Valsdottir ◽  
Jean-Paul Javerzat ◽  
Kevin G. Hardwick
Keyword(s):  
Schizosaccharomyces Pombe ◽  
Fission Yeast ◽  
Chromosome Segregation ◽  
Chromatin Immunoprecipitation ◽  
Spindle Checkpoint ◽  
Central Domain ◽  
Checkpoint Response ◽  
Terminal Domain ◽  
Microtubule Attachment ◽  
Lines Of Evidence

ABSTRACT Several lines of evidence suggest that kinetochores are organizing centers for the spindle checkpoint response and the synthesis of a “wait anaphase” signal in cases of incomplete or improper kinetochore-microtubule attachment. Here we characterize Schizosaccharomyces pombe Bub3p and study the recruitment of spindle checkpoint components to kinetochores. We demonstrate by chromatin immunoprecipitation that they all interact with the central domain of centromeres, consistent with their role in monitoring kinetochore-microtubule interactions. Bub1p and Bub3p are dependent upon one another, but independent of the Mad proteins, for their kinetochore localization. We demonstrate a clear role for the highly conserved N-terminal domain of Bub1p in the robust targeting of Bub1p, Bub3p, and Mad3p to kinetochores and show that this is crucial for an efficient checkpoint response. Surprisingly, neither this domain nor kinetochore localization is required for other functions of Bub1p in chromosome segregation.

Different roles for the stress-activated protein kinase pathway in the regulation of trehalose metabolism in Schizosaccharomyces pombe

Microbiology ◽  
2003 ◽  
Vol 149 (7) ◽  
pp. 1745-1752 ◽  
Author(s):  
V. Paredes ◽  
A. Franco ◽  
T. Soto ◽  
J. Vicente-Soler ◽  
M. Gacto ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Protein Kinase ◽  
Osmotic Stress ◽  
Schizosaccharomyces Pombe ◽  
Fission Yeast ◽  
Stress Responses ◽  
Mitogen Activated Protein Kinase ◽  
Wide Range ◽  
Trehalose Metabolism

The Wis1p-Sty1p mitogen-activated protein kinase cascade is a major signalling system in the fission yeast Schizosaccharomyces pombe for a wide range of stress responses. It is known that trehalose functions as a protective metabolite to counteract deleterious effects of environmental stresses. Herein it is reported that the expression of genes related to trehalose metabolism in S. pombe, ntp1 + (neutral trehalase) and tps1 + [trehalose-6-phosphate (T6P) synthase], is partially regulated by the Sty1p kinase under salt-induced osmotic stress and conditions of slight oxidative stress and is fully dependent on this kinase under severe oxidative stress. This control is carried out through transcription factors Atf1p/Pcr1p during osmotic stress and through Pap1p during exposure to low levels of oxidative stress. However, all three transcription factors are needed for gene expression under conditions of extreme oxidative stress. In addition, a role for Sty1p in the modulation of post-transcriptional activation of trehalase mediated by Pka1p/Sck1p kinases, as well as in the activity of T6P synthase under such stressful conditions has been demonstrated. These results reveal a novel dual action of the Wis1p-Sty1p pathway in the regulation of trehalose metabolism in fission yeast.

scholarly journals Organization, primary structure, and evolution of histone H2A and H2B genes of the fission yeast Schizosaccharomyces pombe.

1985 ◽  
Vol 5 (11) ◽  
pp. 3261-3269 ◽  
Author(s):  
J Choe ◽  
T Schuster ◽  
M Grunstein
Keyword(s):  
Amino Acid ◽  
Schizosaccharomyces Pombe ◽  
Fission Yeast ◽  
Dna Sequences ◽  
Sequence Evolution ◽  
Hydrophobic Core ◽  
Histone H2a ◽  
Acid Protein ◽  
Close Proximity ◽  
Pair Sequence

The histone H2A and H2B genes of the fission yeast Schizosaccharomyces pombe were cloned and sequenced. Southern blot and sequence analyses showed that, unlike other eucaryotes, Saccharomyces cerevisiae included, S. pombe has unequal numbers of these genes, containing two histone H2A genes (H2A-alpha and -beta) and only one H2B gene (H2B-alpha) per haploid genome. H2A- and H2B-alpha are adjacent to each other and are divergently transcribed. H2A-beta has no other histone gene in close proximity. Preceding both H2A-alpha and -beta is a highly conserved 19-base-pair sequence (5'-CATCAC/AAACCCTAACCCTG-3'). The H2A DNA sequences encode two histone H2A subtypes differing in amino acid sequence (three residues) and size (H2A-alpha, 131 residues; H2A-beta, 130 residues). H2B-alpha codes for a 125-amino-acid protein. Sequence evolution is extensive between S. pombe and S. cerevisiae and displays unique patterns of divergence. Certain N-terminal sequences normally divergent between eucaryotes are conserved between the two yeasts. In contrast, the normally conserved hydrophobic core of H2A is as divergent between the yeasts as between S. pombe and calf.

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