scholarly journals CHROMOSOME MICROMANIPULATION

1969 ◽  
Vol 43 (1) ◽  
pp. 40-50 ◽  
Author(s):  
R. Bruce Nicklas ◽  
Carol A. Koch
Keyword(s):  
Chromosome Segregation ◽  
Normal Chromosome ◽  
Chromosome Distribution ◽  
Critical Process ◽  
Spindle Fibers

Kinetochore reorientation is the critical process ensuring normal chromosome distribution. Reorientation has been studied in living grasshopper spermatocytes, in which bivalents with both chromosomes oriented to the same pole (unipolar orientation) occur but are unstable: sooner or later one chromosome reorients, the stable, bipolar orientation results, and normal anaphase segregation to opposite poles follows. One possible source of stability in bipolar orientations is the normal spindle forces toward opposite poles, which slightly stretch the bivalent. This tension is lacking in unipolar orientations because all the chromosomal spindle fibers and spindle forces are directed toward one pole. The possible role of tension has been tested directly by micromanipulation of bivalents in unipolar orientation to artificially create the missing tension. Without exception, such bivalents never reorient before the tension is released; a total time "under tension" of over 5 hr has been accumulated in experiments on eight bivalents in eight cells. In control experiments these same bivalents reoriented from a unipolar orientation within 16 min, on the average, in the absence of tension. Controlled reorientation and chromosome segregation can be explained from the results of these and related experiments.

Meiotic CENP-C is a shepherd: bridging the space between the centromere and the kinetochore in time and space

2020 ◽  
Vol 64 (2) ◽  
pp. 251-261
Author(s):  
Jessica E. Fellmeth ◽  
Kim S. McKim
Keyword(s):  
Chromosome Segregation ◽  
New Technologies ◽  
Early Prophase ◽  
Unique Role ◽  
Kinetochore Assembly ◽  
M Phase ◽  
In Vivo Analysis ◽  
Meiosis I

Abstract While many of the proteins involved in the mitotic centromere and kinetochore are conserved in meiosis, they often gain a novel function due to the unique needs of homolog segregation during meiosis I (MI). CENP-C is a critical component of the centromere for kinetochore assembly in mitosis. Recent work, however, has highlighted the unique features of meiotic CENP-C. Centromere establishment and stability require CENP-C loading at the centromere for CENP-A function. Pre-meiotic loading of proteins necessary for homolog recombination as well as cohesion also rely on CENP-C, as do the main scaffolding components of the kinetochore. Much of this work relies on new technologies that enable in vivo analysis of meiosis like never before. Here, we strive to highlight the unique role of this highly conserved centromere protein that loads on to centromeres prior to M-phase onset, but continues to perform critical functions through chromosome segregation. CENP-C is not merely a structural link between the centromere and the kinetochore, but also a functional one joining the processes of early prophase homolog synapsis to late metaphase kinetochore assembly and signaling.

scholarly journals The Role of Cdh1p in Maintaining Genomic Stability in Budding Yeast

Genetics ◽  
2003 ◽  
Vol 165 (2) ◽  
pp. 489-503 ◽  
Author(s):  
Karen E Ross ◽  
Orna Cohen-Fix
Keyword(s):  
Cell Cycle ◽  
Chromosome Segregation ◽  
Spindle Assembly Checkpoint ◽  
Chromosome Loss ◽  
Cyclin Dependent Kinase ◽  
Anaphase Promoting Complex ◽  
Growth Defects ◽  
Genes Encoding ◽  
Specificity Factor

Abstract Cdh1p, a substrate specificity factor for the cell cycle-regulated ubiquitin ligase, the anaphase-promoting complex/cyclosome (APC/C), promotes exit from mitosis by directing the degradation of a number of proteins, including the mitotic cyclins. Here we present evidence that Cdh1p activity at the M/G1 transition is important not only for mitotic exit but also for high-fidelity chromosome segregation in the subsequent cell cycle. CDH1 showed genetic interactions with MAD2 and PDS1, genes encoding components of the mitotic spindle assembly checkpoint that acts at metaphase to prevent premature chromosome segregation. Unlike cdh1Δ and mad2Δ single mutants, the mad2Δ cdh1Δ double mutant grew slowly and exhibited high rates of chromosome and plasmid loss. Simultaneous deletion of PDS1 and CDH1 caused extensive chromosome missegregation and cell death. Our data suggest that at least part of the chromosome loss can be attributed to kinetochore/spindle problems. Our data further suggest that Cdh1p and Sic1p, a Cdc28p/Clb inhibitor, have overlapping as well as nonoverlapping roles in ensuring proper chromosome segregation. The severe growth defects of both mad2Δ cdh1Δ and pds1Δ cdh1Δ strains were rescued by overexpressing Swe1p, a G2/M inhibitor of the cyclin-dependent kinase, Cdc28p/Clb. We propose that the failure to degrade cyclins at the end of mitosis leaves cdh1Δ mutant strains with abnormal Cdc28p/Clb activity that interferes with proper chromosome segregation.

scholarly journals Bub1 mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis

2007 ◽  
Vol 179 (2) ◽  
pp. 255-267 ◽  
Author(s):  
Karthik Jeganathan ◽  
Liviu Malureanu ◽  
Darren J. Baker ◽  
Susan C. Abraham ◽  
Jan M. van Deursen
Keyword(s):  
Cell Death ◽  
Chromosome Segregation ◽  
Physiological Role ◽  
Mitotic Checkpoint ◽  
Critical Threshold ◽  
Wild Type ◽  
Checkpoint Protein ◽  
Chromosome Missegregation ◽  
Mitotic Checkpoint Protein

The physiological role of the mitotic checkpoint protein Bub1 is unknown. To study this role, we generated a series of mutant mice with a gradient of reduced Bub1 expression using wild-type, hypomorphic, and knockout alleles. Bub1 hypomorphic mice are viable, fertile, and overtly normal despite weakened mitotic checkpoint activity and high percentages of aneuploid cells. Bub1 haploinsufficient mice, which have a milder reduction in Bub1 protein than Bub1 hypomorphic mice, also exhibit reduced checkpoint activity and increased aneuploidy, but to a lesser extent. Although cells from Bub1 hypomorphic and haploinsufficient mice have similar rates of chromosome missegregation, cell death after an aberrant separation decreases dramatically with declining Bub1 levels. Importantly, Bub1 hypomorphic mice are highly susceptible to spontaneous tumors, whereas Bub1 haploinsufficient mice are not. These findings demonstrate that loss of Bub1 below a critical threshold drives spontaneous tumorigenesis and suggest that in addition to ensuring proper chromosome segregation, Bub1 is important for mediating cell death when chromosomes missegregate.

Persisting demibivalents: a unique meiotic behaviour in Cuscuta babylonica Choisy

Genome ◽  
1987 ◽  
Vol 29 (1) ◽  
pp. 63-66 ◽  
Author(s):  
Batia Pazy ◽  
Uzi Plitmann
Keyword(s):  
Key Words ◽  
Chromosome Segregation ◽  
Meiotic Behaviour ◽  
Chromosome Behaviour ◽  
Chromosome Movement ◽  
Pollen Mother Cells ◽  
Key Words Meiosis ◽  
Mother Cells ◽  
Telomeric Association

Idiosyncratic chromosome behaviour during meiosis was found in pollen mother cells of Cuscuta babylonica Choisy, a thread-like holoparasitic herb. Its main features are among the following: (i) telomeric association between homologues through most stages of the process, which leads to persisting chromatid bivalents (= "demibivalents"); (ii) uncommon chromosome segregation in first and second anaphase; and (iii) prolonged intensified heterochromatinization. Although "regular" in its own way, this process leads to the formation of unviable products. Its further investigation might contribute to our understanding of the role of the spindle and chromosome movement in the ordinary process of meiosis. Key words: meiosis (abnormal), persisting demibivalents, Cuscuta babylonica.

fumble Encodes a Pantothenate Kinase Homolog Required for Proper Mitosis and Meiosis in Drosophila melanogaster

Genetics ◽  
2001 ◽  
Vol 157 (3) ◽  
pp. 1267-1276
Author(s):  
Katayoun Afshar ◽  
Pierre Gönczy ◽  
Stephen DiNardo ◽  
Steven A Wasserman
Keyword(s):  
Cell Division ◽  
Chromosome Segregation ◽  
Cell Division Cycle ◽  
Protein Isoforms ◽  
Pantothenate Kinase ◽  
Male Germline ◽  
Dividing Cells ◽  
Mutant Cells ◽  
Mitosis And Meiosis

Abstract A number of fundamental processes comprise the cell division cycle, including spindle formation, chromosome segregation, and cytokinesis. Our current understanding of these processes has benefited from the isolation and analysis of mutants, with the meiotic divisions in the male germline of Drosophila being particularly well suited to the identification of the required genes. We show here that the fumble (fbl) gene is required for cell division in Drosophila. We find that dividing cells in fbl-deficient testes exhibit abnormalities in bipolar spindle organization, chromosome segregation, and contractile ring formation. Cytological analysis of larval neuroblasts from null mutants reveals a reduced mitotic index and the presence of polyploid cells. Molecular analysis demonstrates that fbl encodes three protein isoforms, all of which contain a domain with high similarity to the pantothenate kinases of A. nidulans and mouse. The largest Fumble isoform is dispersed in the cytoplasm during interphase, concentrates around the spindle at metaphase, and localizes to the spindle midbody at telophase. During early embryonic development, the protein localizes to areas of membrane deposition and/or rearrangement, such as the metaphase and cellularization furrows. Given the role of pantothenate kinase in production of Coenzyme A and in phospholipid biosynthesis, this pattern of localization is suggestive of a role for fbl in membrane synthesis. We propose that abnormalities in synthesis and redistribution of membranous structures during the cell division cycle underlie the cell division defects in fbl mutant cells.

Coming of age in Milano: Ermanno Olmi from sponsored cinema to feature filmmaking

2021 ◽  
Vol 9 (3) ◽  
pp. 411-428
Author(s):  
Jim Carter
Keyword(s):  
Coming Of Age ◽  
Italian Cinema ◽  
Modern Life ◽  
Cinema Studies ◽  
The Past ◽  
Michelangelo Antonioni ◽  
Feature Films ◽  
Bernardo Bertolucci ◽  
Critical Process

This article argues that a full understanding of Ermanno Olmi’s feature films will require a deep engagement with the sponsored cinema he made as director of the Sezione Cinema Edisonvolta. It begins by spelling out some of the stakes and challenges of a ‘sponsored turn’ in Italian cinema studies, which during the past decade has inaugurated the long archival and critical process of revaluing the corporate roots of auteurs like Michelangelo Antonioni, Bernardo Bertolucci and, to a certain extent, Ermanno Olmi. It then elaborates on the relation between Olmi’s sponsored cinema (1953–61) and feature filmmaking (1961–2014) by analysing two films that mark the director’s transition from the small to big screen: Michelino 1 a B (1956) and Il posto (1961). The central contention is that these films tell two different versions of the same coming-of-age story: a young boy from the provinces finds work in a downtown office building, where he must come to terms with the fact that he will remain there all his life. The distance between the two films is a measure of Olmi’s own coming-of-age as an intellectual: from a resolved promoter of the guiding role of business in modern life to a sceptical interrogator of white-collar mundanity. After a comparative reading that reveals general similarities of structure and specific scenes of quotation, the article concludes with some remarks about education, a concept through which Olmi’s feature films show themselves to be aware of – even commenting on – sponsored cinema.

scholarly journals Aurora B kinase activity is regulated by SET/TAF1 on Sgo2 at the inner centromere

2019 ◽  
Vol 218 (10) ◽  
pp. 3223-3236 ◽  
Author(s):  
Yuichiro Asai ◽  
Koh Fukuchi ◽  
Yuji Tanno ◽  
Saki Koitabashi-Kiyozuka ◽  
Tatsuyuki Kiyozuka ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Chromosomal Instability ◽  
Kinase Activity ◽  
Fine Tuning ◽  
Aurora B ◽  
The Novel ◽  
Aurora B Kinase ◽  
Microtubule Attachment ◽  
Molecular Events

The accurate regulation of phosphorylation at the kinetochore is essential for establishing chromosome bi-orientation. Phosphorylation of kinetochore proteins by the Aurora B kinase destabilizes improper kinetochore–microtubule attachments, whereas the phosphatase PP2A has a counteracting role. Imbalanced phosphoregulation leads to error-prone chromosome segregation and aneuploidy, a hallmark of cancer cells. However, little is known about the molecular events that control the balance of phosphorylation at the kinetochore. Here, we show that localization of SET/TAF1, an oncogene product, to centromeres maintains Aurora B kinase activity by inhibiting PP2A, thereby correcting erroneous kinetochore–microtubule attachment. SET localizes at the inner centromere by interacting directly with shugoshin 2, with SET levels declining at increased distances between kinetochore pairs, leading to establishment of chromosome bi-orientation. Moreover, SET overexpression induces chromosomal instability by disrupting kinetochore–microtubule attachment. Thus, our findings reveal the novel role of SET in fine-tuning the phosphorylation level at the kinetochore by balancing the activities of Aurora B and PP2A.

scholarly journals Phosphorylation of Drosophila CENP-A on serine 20 regulates protein turn-over and centromere-specific loading

2019 ◽  
Vol 47 (20) ◽  
pp. 10754-10770 ◽  
Author(s):  
Anming Huang ◽  
Leopold Kremser ◽  
Fabian Schuler ◽  
Doris Wilflingseder ◽  
Herbert Lindner ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Posttranslational Modifications ◽  
Centromeric Chromatin ◽  
Phosphorylated Form ◽  
Specific Loading ◽  
Histone H3 Variant ◽  
Proteasome Pathway ◽  
Turn Over ◽  
Fine Tune

Abstract Centromeres are specialized chromosomal regions epigenetically defined by the presence of the histone H3 variant CENP-A. CENP-A is required for kinetochore formation which is essential for chromosome segregation during mitosis. Spatial restriction of CENP-A to the centromere is tightly controlled. Its overexpression results in ectopic incorporation and the formation of potentially deleterious neocentromeres in yeast, flies and in various human cancers. While the contribution of posttranslational modifications of CENP-A to these processes has been studied in yeast and mammals to some extent, very little is known about Drosophila melanogaster. Here, we show that CENP-A is phosphorylated at serine 20 (S20) by casein kinase II and that in mitotic cells, the phosphorylated form is enriched on chromatin. Importantly, our results reveal that S20 phosphorylation regulates the turn-over of prenucleosomal CENP-A by the SCFPpa-proteasome pathway and that phosphorylation promotes removal of CENP-A from ectopic but not from centromeric sites in chromatin. We provide multiple lines of evidence for a crucial role of S20 phosphorylation in controlling restricted incorporation of CENP-A into centromeric chromatin in flies. Modulation of the phosphorylation state of S20 may provide the cells with a means to fine-tune CENP-A levels in order to prevent deleterious loading to extra-centromeric sites.

scholarly journals Phase separation of Polo-like kinase 4 by autoactivation and clustering drives centriole biogenesis

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Jung-Eun Park ◽  
Liang Zhang ◽  
Jeong Kyu Bang ◽  
Thorkell Andresson ◽  
Frank DiMaio ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Phase Separation ◽  
Symmetry Breaking ◽  
Genomic Instability ◽  
Chromosome Segregation ◽  
Genomic Stability ◽  
Normal Chromosome ◽  
Tight Control ◽  
Centriole Duplication ◽  
Disordered Loop

Abstract Tight control of centriole duplication is critical for normal chromosome segregation and the maintenance of genomic stability. Polo-like kinase 4 (Plk4) is a key regulator of centriole biogenesis. How Plk4 dynamically promotes its symmetry-breaking relocalization and achieves its procentriole-assembly state remains unknown. Here we show that Plk4 is a unique kinase that utilizes its autophosphorylated noncatalytic cryptic polo-box (CPB) to phase separate and generate a nanoscale spherical condensate. Analyses of the crystal structure of a phospho-mimicking, condensation-proficient CPB mutant reveal that a disordered loop at the CPB PB2-tip region is critically required for Plk4 to generate condensates and induce procentriole assembly. CPB phosphorylation also promotes Plk4’s dissociation from the Cep152 tether while binding to downstream STIL, thus allowing Plk4 condensate to serve as an assembling body for centriole biogenesis. This study uncovers the mechanism underlying Plk4 activation and may offer strategies for anti-Plk4 intervention against genomic instability and cancer.

scholarly journals Mammalian Protein SCP1 Forms Synaptonemal Complex-like Structures in the Absence of Meiotic Chromosomes

2005 ◽  
Vol 16 (1) ◽  
pp. 212-217 ◽  
Author(s):  
Rupert Öllinger ◽  
Manfred Alsheimer ◽  
Ricardo Benavente
Keyword(s):  
Chromosome Segregation ◽  
Meiotic Prophase ◽  
Experimental Conditions ◽  
Homologous Chromosomes ◽  
Meiotic Chromosomes ◽  
Heterologous System ◽  
Primary Determinant ◽  
Specific Proteins ◽  
Mammalian Protein

Synaptonemal complexes (SCs) are evolutionary conserved, meiosis-specific structures that play a central role in synapsis of homologous chromosomes, chiasmata distribution, and chromosome segregation. However, it is still for the most part unclear how SCs do assemble during meiotic prophase. Major components of mammalian SCs are the meiosis-specific proteins SCP1, 2, and 3. To investigate the role of SCP1 in SC assembly, we expressed SCP1 in a heterologous system, i.e., in COS-7 cells that normally do not express SC proteins. Notably, under these experimental conditions SCP1 is able to form structures that closely resemble SCs (i.e., polycomplexes). Moreover, we show that mutations that modify the length of the central α-helical domain of SCP1 influence the width of polycomplexes. Finally, we demonstrate that deletions of the nonhelical N- or C-termini both affect polycomplex assembly, although in a different manner. We conclude that SCP1 is a primary determinant of SC assembly that plays a key role in synapsis of homologous chromosomes.

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