Switching the centromeres on and off: epigenetic chromatin alterations provide plasticity in centromere activity stabilizing aberrant dicentric chromosomes

2013 ◽  
Vol 41 (6) ◽  
pp. 1648-1653 ◽  
Author(s):  
Hiroshi Sato ◽  
Shigeaki Saitoh
Keyword(s):  
Fission Yeast ◽  
Chromosome Breakage ◽  
Chromosomal Locus ◽  
Single Chromosome ◽  
Dicentric Chromosomes ◽  
Cycle Arrest ◽  
Intrinsic Mechanism ◽  
Centromere Inactivation ◽  
Mitosis And Meiosis ◽  
Active Centromere

The kinetochore, which forms on a specific chromosomal locus called the centromere, mediates interactions between the chromosome and the spindle during mitosis and meiosis. Abnormal chromosome rearrangements and/or neocentromere formation can cause the presence of multiple centromeres on a single chromosome, which results in chromosome breakage or cell cycle arrest. Analyses of artificial dicentric chromosomes suggested that the activity of the centromere is regulated epigenetically; on some stably maintained dicentric chromosomes, one of the centromeres no longer functions as a platform for kinetochore formation, although the DNA sequence remains intact. Such epigenetic centromere inactivation occurs in cells of various eukaryotes harbouring ‘regional centromeres’, such as those of maize, fission yeast and humans, suggesting that the position of the active centromere is determined by epigenetic markers on a chromosome rather than the nucleotide sequence. Our recent findings in fission yeast revealed that epigenetic centromere inactivation consists of two steps: disassembly of the kinetochore initiates inactivation and subsequent heterochromatinization prevents revival of the inactivated centromere. Kinetochore disassembly followed by heterochromatinization is also observed in normal senescent human cells. Thus epigenetic centromere inactivation may not only stabilize abnormally generated dicentric chromosomes, but also be part of an intrinsic mechanism regulating cell proliferation.

scholarly journals Two Related Kinesins,klp5+andklp6+, Foster Microtubule Disassembly and Are Required for Meiosis in Fission Yeast

2001 ◽  
Vol 12 (12) ◽  
pp. 3919-3932 ◽  
Author(s):  
Robert R. West ◽  
Terra Malmstrom ◽  
Cynthia L. Troxell ◽  
J. Richard McIntosh
Keyword(s):  
Cell Cycle ◽  
Fission Yeast ◽  
Amino Terminal ◽  
Cellular Processes ◽  
Cycle Arrest ◽  
Microtubule Motor ◽  
Cytoplasmic Microtubules ◽  
High Concentrations ◽  
Kinesin Superfamily ◽  
Mitosis And Meiosis

The kinesin superfamily of microtubule motor proteins is important in many cellular processes, including mitosis and meiosis, vesicle transport, and the establishment and maintenance of cell polarity. We have characterized two related kinesins in fission yeast,klp5+andklp6+, that are amino-terminal motors of the KIP3 subfamily. Analysis of null mutants demonstrates that neither klp5+norklp6+, individually or together, is essential for vegetative growth, although these mutants have altered microtubule behavior. klp5Δ and klp6Δ are resistant to high concentrations of the microtubule poison thiabendazole and have abnormally long cytoplasmic microtubules that can curl around the ends of the cell. This phenotype is greatly enhanced in the cell cycle mutant cdc25–22, leading to a bent, asymmetric cell morphology as cells elongate during cell cycle arrest. Klp5p-GFP and Klp6p-GFP both localize to cytoplasmic microtubules throughout the cell cycle and to spindles in mitosis, but their localizations are not interdependent. During the meiotic phase of the life cycle, both of these kinesins are essential. Spore viability is low in homozygous crosses of either null mutant. Heterozygous crosses of klp5Δ with klp6Δ have an intermediate viability, suggesting cooperation between these proteins in meiosis.

scholarly journals Slm9, a Novel Nuclear Protein Involved in Mitotic Control in Fission Yeast

Genetics ◽  
2000 ◽  
Vol 155 (2) ◽  
pp. 623-631
Author(s):  
Junko Kanoh ◽  
Paul Russell
Keyword(s):  
Cell Cycle ◽  
Fission Yeast ◽  
Cell Elongation ◽  
Nuclear Protein ◽  
G1 Arrest ◽  
Permissive Temperature ◽  
Cdc2 Kinase ◽  
Synthetic Lethal ◽  
Cycle Arrest ◽  
Novel Protein

Abstract In the fission yeast Schizosaccharomyces pombe, as in other eukaryotic cells, Cdc2/cyclin B complex is the key regulator of mitosis. Perhaps the most important regulation of Cdc2 is the inhibitory phosphorylation of tyrosine-15 that is catalyzed by Wee1 and Mik1. Cdc25 and Pyp3 phosphatases dephosphorylate tyrosine-15 and activate Cdc2. To isolate novel activators of Cdc2 kinase, we screened synthetic lethal mutants in a cdc25-22 background at the permissive temperature (25°). One of the genes, slm9, encodes a novel protein of 807 amino acids. Slm9 is most similar to Hir2, the histone gene regulator in budding yeast. Slm9 protein level is constant and Slm9 is localized to the nucleus throughout the cell cycle. The slm9 disruptant is delayed at the G2-M transition as indicated by cell elongation and analysis of DNA content. Inactivation of Wee1 fully suppressed the cell elongation phenotype caused by the slm9 mutation. The slm9 mutant is defective in recovery from G1 arrest after nitrogen starvation. The slm9 mutant is also UV sensitive, showing a defect in recovery from the cell cycle arrest after UV irradiation.

scholarly journals Fission Yeast Rad26 Is a Regulatory Subunit of the Rad3 Checkpoint Kinase

2002 ◽  
Vol 13 (2) ◽  
pp. 480-492 ◽  
Author(s):  
Tom D. Wolkow ◽  
Tamar Enoch
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Fission Yeast ◽  
Complex Analysis ◽  
Kinase Activity ◽  
Regulatory Subunit ◽  
Kinase Activation ◽  
Checkpoint Proteins ◽  
Cycle Arrest ◽  
Phosphoinositide 3 Kinase

Fission yeast Rad3 is a member of a family of phosphoinositide 3-kinase -related kinases required for the maintenance of genomic stability in all eukaryotic cells. In fission yeast, Rad3 regulates the cell cycle arrest and recovery activities associated with the G2/M checkpoint. We have developed an assay that directly measures Rad3 kinase activity in cells expressing physiological levels of the protein. Using the assay, we demonstrate directly that Rad3 kinase activity is stimulated by checkpoint signals. Of the five other G2/M checkpoint proteins (Hus1, Rad1, Rad9, Rad17, and Rad26), only Rad26 was required for Rad3 kinase activity. Because Rad26 has previously been shown to interact constitutively with Rad3, our results demonstrate that Rad26 is a regulatory subunit, and Rad3 is the catalytic subunit, of the Rad3/Rad26 kinase complex. Analysis of Rad26/Rad3 kinase activation in rad26.T12, a mutant that is proficient for cell cycle arrest, but defective in recovery, suggests that these two responses to checkpoint signals require quantitatively different levels of kinase activity from the Rad3/Rad26 complex.

HZwint-1, a novel human kinetochore component that interacts with HZW10

2000 ◽  
Vol 113 (11) ◽  
pp. 1939-1950 ◽  
Author(s):  
D.A. Starr ◽  
R. Saffery ◽  
Z. Li ◽  
A.E. Simpson ◽  
K.H. Choo ◽  
...  
Keyword(s):  
Hela Cells ◽  
Coiled Coil ◽  
Yeast Two Hybrid ◽  
Interacting Protein ◽  
Dicentric Chromosomes ◽  
Centromere Function ◽  
Coiled Coil Domain ◽  
Gfp Fluorescence ◽  
Two Hybrid ◽  
Active Centromere

HZwint-1 (Human ZW10 interacting protein-1) was identified in a yeast two hybrid screen for proteins that interact with HZW10. HZwint-1 cDNA encodes a 43 kDa protein predicted to contain an extended coiled-coil domain. Immunofluorescence studies with sera raised against HZwint-1 protein revealed strong kinetochore staining in nocodazole-arrested chromosome spreads. This signal co-localizes at the kinetochore with HZW10, at a position slightly outside of the central part of the centromere as revealed by staining with a CREST serum. The kinetochore localization of HZwint-1 has been confirmed by following GFP fluorescence in HeLa cells transiently transfected with a plasmid encoding a GFP/HZwint-1 fusion protein. In cycling HeLa cells, HZwint-1 localizes to the kinetochore of prophase HeLa cells prior to HZW10 localization, and remains at the kinetochore until late in anaphase. This localization pattern, combined with the two-hybrid results, suggests that HZwint-1 may play a role in targeting HZW10 to the kinetochore at prometaphase. HZwint-1 was also found to localize to neocentromeres and to the active centromere of dicentric chromosomes. HZwint-1 thus appears to associate with all active centromeres, implying that it plays an important role in correct centromere function.

scholarly journals Loss of centromere function drives karyotype evolution in closely related Malassezia species

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Sundar Ram Sankaranarayanan ◽  
Giuseppe Ianiri ◽  
Marco A Coelho ◽  
Md Hashim Reza ◽  
Bhagya C Thimmappa ◽  
...  
Keyword(s):  
Chromosome Number ◽  
Histone H3 ◽  
Chromosome Breakage ◽  
Ancestral State ◽  
Chromosome Fusion ◽  
Closely Related Species ◽  
Malassezia Species ◽  
Malassezia Globosa ◽  
Centromere Inactivation ◽  
Genome Assemblies

Genomic rearrangements associated with speciation often result in variation in chromosome number among closely related species. Malassezia species show variable karyotypes ranging between six and nine chromosomes. Here, we experimentally identified all eight centromeres in M. sympodialis as 3–5-kb long kinetochore-bound regions that span an AT-rich core and are depleted of the canonical histone H3. Centromeres of similar sequence features were identified as CENP-A-rich regions in Malassezia furfur, which has seven chromosomes, and histone H3 depleted regions in Malassezia slooffiae and Malassezia globosa with nine chromosomes each. Analysis of synteny conservation across centromeres with newly generated chromosome-level genome assemblies suggests two distinct mechanisms of chromosome number reduction from an inferred nine-chromosome ancestral state: (a) chromosome breakage followed by loss of centromere DNA and (b) centromere inactivation accompanied by changes in DNA sequence following chromosome–chromosome fusion. We propose that AT-rich centromeres drive karyotype diversity in the Malassezia species complex through breakage and inactivation.

Cytogenetic stability of aneuploid maize tissue cultures

1986 ◽  
Vol 28 (3) ◽  
pp. 374-384 ◽  
Author(s):  
C. A. Rhodes ◽  
R. L. Phillips ◽  
C. E. Green
Keyword(s):  
Cell Walls ◽  
Chromosome Breakage ◽  
Pollen Sterility ◽  
Tissue Cultures ◽  
Culture Initiation ◽  
Single Chromosome ◽  
Recessive Mutations ◽  
Regenerated Plants ◽  
Genetic Stocks ◽  
Common Cell

Monosomic maize tissue cultures might be used to select recessive mutations of cellular traits. This strategy would avoid some of the problems encountered with haploid cultures such as lack of vigor, sterility of regenerated plants, and uncontrolled diploidization. Monosomic and other aneuploid plants were selected among progeny of W22 R/r-x1 crossed with genetic stocks containing recessive markers. The r-x1 allele induces aneuploidy at a frequency of about 15%. Immature tassels of selected plants were used to initiate totipotent tissue cultures. Plants were regenerated from the cultures over a period of 3 to 17 months after culture initiation. Meiotic karyotypes of microsporocytes and pollen sterility were analyzed in regenerated plants. At least 40% of the 161 plants regenerated from aneuploid cultures had altered karyotypes. This frequency was not related to culture age. Most alterations involved chromosome breakage rather than changes in chromosome number. Types of alterations included heteromorphic pairs (18.1%), translocations (12.5%), addition (10.6%) or loss (1.4%) of chromosomes, and genomic doubling (2.8%). Four euploid cultures, including one with a translocation, were equally unstable (49% with alterations among 115 plants). Euploid cultures gave rise to plants with translocations (12.3%), heteromorphic pairs (8.8%), and genomic doubling (29.2%), but no single chromosome additions or losses. Plants that shared a common distinctive karyotype, such as a specific translocation, were probably derived from a common cell line. Tassels with sectors of two different karyotypes were frequent in plants regenerated from aneuploid (20%) or euploid (33%) cultures. Coenocytic microsporocytes, which lacked cell walls between nuclei, were found in plants from monosomic-2, deficient-2L, and monosomic-6 cultures. Another aberration (23% of 144 regenerants) was lack of cell wall formation after the first and (or) second meiotic division, which was often followed by nuclear fusion. Karyotypic changes observed in this study rarely involved the monosomic chromosome, which means that monosomic tissue cultures could be used to select recessive mutants. Further tests would be needed to demonstrate that the selected gene resides in the monosomic chromosome.Key words: Zea mays, monosomic, trisomic, chromosome, somaclonal variation, karyotype.

Components of the human spindle checkpoint control mechanism localize specifically to the active centromere on dicentric chromosomes

2000 ◽  
Vol 107 (4) ◽  
pp. 376-384 ◽  
Author(s):  
Richard Saffery ◽  
Danielle Irvine ◽  
Belinda Griffiths ◽  
Paul Kalitsis ◽  
K. Choo
Keyword(s):  
Control Mechanism ◽  
Spindle Checkpoint ◽  
Checkpoint Control ◽  
Dicentric Chromosomes ◽  
Active Centromere

scholarly journals The Role of the RACK1 Ortholog Cpc2p in Modulating Pheromone-Induced Cell Cycle Arrest in Fission Yeast

PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e65927 ◽  
Author(s):  
Magdalena Mos ◽  
Manuel A. Esparza-Franco ◽  
Emma L. Godfrey ◽  
Kathryn Richardson ◽  
John Davey ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Fission Yeast ◽  
Cycle Arrest

scholarly journals The Role of Dicentric Chromosome Formation and Secondary Centromere Deletion in the Evolution of Myeloid Malignancy

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Ruth N. MacKinnon ◽  
Lynda J. Campbell
Keyword(s):  
Cancer Cells ◽  
Genome Instability ◽  
Chromosome Organization ◽  
Myeloid Malignancy ◽  
Dicentric Chromosomes ◽  
Cancer Genomes ◽  
Cancer Initiation ◽  
Centromere Inactivation ◽  
Chromosome Formation

Dicentric chromosomes have been identified as instigators of the genome instability associated with cancer, but this instability is often resolved by one of a number of different secondary events. These include centromere inactivation, inversion, and intercentromeric deletion. Deletion or excision of one of the centromeres may be a significant occurrence in myeloid malignancy and other malignancies but has not previously been widely recognized, and our reports are the first describing centromere deletion in cancer cells. We review what is known about dicentric chromosomes and the mechanisms by which they can undergo stabilization in both constitutional and cancer genomes. The failure to identify centromere deletion in cancer cells until recently can be partly explained by the standard approaches to routine diagnostic cancer genome analysis, which do not identify centromeres in the context of chromosome organization. This hitherto hidden group of primary dicentric, secondary monocentric chromosomes, together with other unrecognized dicentric chromosomes, points to a greater role for dicentric chromosomes in cancer initiation and progression than is generally acknowledged. We present a model that predicts and explains a significant role for dicentric chromosomes in the formation of unbalanced translocations in malignancy.

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