scholarly journals A Chromatin-associated Kinesin-related Protein Required for Normal Mitotic Chromosome Segregation in Drosophila

1997 ◽  
Vol 139 (6) ◽  
pp. 1361-1371 ◽  
Author(s):  
Isabel Molina ◽  
Sigrid Baars ◽  
Julie A. Brill ◽  
Karen G. Hales ◽  
Margaret T. Fuller ◽  
...  
Keyword(s):  
Cell Division ◽  
Gene Product ◽  
Chromosome Segregation ◽  
Mitotic Chromosome ◽  
Related Protein ◽  
Wild Type ◽  
Type Function ◽  
Microtubule Motor ◽  
Mitotic Figures ◽  
Bipolar Spindles

The tiovivo (tio) gene of Drosophila encodes a kinesin-related protein, KLP38B, that colocalizes with condensed chromatin during cell division. Wild-type function of the tio gene product KLP38B is required for normal chromosome segregation during mitosis. Mitotic cells in tio larval brains displayed circular mitotic figures, increased ploidy, and abnormal anaphase figures. KLP38B mRNA is maternally provided and expressed in cells about to undergo division. We propose that KLP38B, perhaps redundantly with other chromosome-associated microtubule motor proteins, contributes to interactions between chromosome arms and microtubules important for establishing bipolar attachment of chromosomes and assembly of stable bipolar spindles.

scholarly journals The human Mis12 complex is required for kinetochore assembly and proper chromosome segregation

2006 ◽  
Vol 173 (1) ◽  
pp. 9-17 ◽  
Author(s):  
Susan L. Kline ◽  
Iain M. Cheeseman ◽  
Tetsuya Hori ◽  
Tatsuo Fukagawa ◽  
Arshad Desai
Keyword(s):  
Cell Division ◽  
Chromosome Segregation ◽  
Essential Role ◽  
Stable Complex ◽  
Wild Type ◽  
Outer Plate ◽  
Checkpoint Protein ◽  
Kinetochore Assembly ◽  
Attachment Sites ◽  
Spindle Microtubules

During cell division, kinetochores form the primary chromosomal attachment sites for spindle microtubules. We previously identified a network of 10 interacting kinetochore proteins conserved between Caenorhabditis elegans and humans. In this study, we investigate three proteins in the human network (hDsn1Q9H410, hNnf1PMF1, and hNsl1DC31). Using coexpression in bacteria and fractionation of mitotic extracts, we demonstrate that these proteins form a stable complex with the conserved kinetochore component hMis12. Human or chicken cells depleted of Mis12 complex subunits are delayed in mitosis with misaligned chromosomes and defects in chromosome biorientation. Aligned chromosomes exhibited reduced centromere stretch and diminished kinetochore microtubule bundles. Consistent with this, localization of the outer plate constituent Ndc80HEC1 was severely reduced. The checkpoint protein BubR1, the fibrous corona component centromere protein (CENP) E, and the inner kinetochore proteins CENP-A and CENP-H also failed to accumulate to wild-type levels in depleted cells. These results indicate that a four-subunit Mis12 complex plays an essential role in chromosome segregation in vertebrates and contributes to mitotic kinetochore assembly.

scholarly journals Prophase removal of chromosome-associated RNAs facilitates anaphase chromosome segregation

2019 ◽  
Author(s):  
Judith A. Sharp ◽  
Wei Wang ◽  
Michael D. Blower
Keyword(s):  
Cell Division ◽  
Chromosome Segregation ◽  
Mitotic Chromosome ◽  
Nuclear Protein ◽  
Aurora B ◽  
Dna Binding Domain ◽  
Nucleic Acid Binding ◽  
Mitotic Chromosomes ◽  
Nuclear Envelope Breakdown ◽  
Binding Domains

AbstractDuring mitosis, the genome is transformed from a decondensed, transcriptionally active state to a highly condensed, transcriptionally inactive state. Mitotic chromosome reorganization is marked by the general attenuation of transcription on chromosome arms, yet how the cell regulates nuclear and chromatin-associated RNAs after chromosome condensation and nuclear envelope breakdown is unknown. SAF-A/hnRNPU is an abundant nuclear protein with RNA-to-DNA tethering activity, coordinated by two spatially distinct nucleic acid binding domains. Here we show that RNA is evicted from prophase chromosomes through Aurora-B-dependent phosphorylation of the SAF-A DNA-binding domain; failure to execute this pathway leads to accumulation of SAF-A:RNA complexes on mitotic chromosomes and elevated rates of anaphase segregation defects. This work reveals a role for Aurora-B in removing chromatin-associated RNAs during prophase, and demonstrates that Aurora-B dependent relocalization of SAF-A during cell division contributes to the fidelity of chromosome segregation.

scholarly journals Mitotic Chromosome Biorientation in Fission Yeast Is Enhanced by Dynein and a Minus-end–directed, Kinesin-like Protein

2007 ◽  
Vol 18 (6) ◽  
pp. 2216-2225 ◽  
Author(s):  
Ekaterina L. Grishchuk ◽  
Ilia S. Spiridonov ◽  
J. Richard McIntosh
Keyword(s):  
Fission Yeast ◽  
Chromosome Segregation ◽  
Mitotic Chromosome ◽  
Spindle Pole ◽  
Ultrastructural Analysis ◽  
Yeast Cells ◽  
Mitotic Spindles ◽  
Wild Type ◽  
Spindle Poles ◽  
Spindle Microtubules

Chromosome biorientation, the attachment of sister kinetochores to sister spindle poles, is vitally important for accurate chromosome segregation. We have studied this process by following the congression of pole-proximal kinetochores and their subsequent anaphase segregation in fission yeast cells that carry deletions in any or all of this organism's minus end–directed, microtubule-dependent motors: two related kinesin 14s (Pkl1p and Klp2p) and dynein. None of these deletions abolished biorientation, but fewer chromosomes segregated normally without Pkl1p, and to a lesser degree without dynein, than in wild-type cells. In the absence of Pkl1p, which normally localizes to the spindle and its poles, the checkpoint that monitors chromosome biorientation was defective, leading to frequent precocious anaphase. Ultrastructural analysis of mutant mitotic spindles suggests that Pkl1p contributes to error-free biorientation by promoting normal spindle pole organization, whereas dynein helps to anchor a focused bundle of spindle microtubules at the pole.

scholarly journals Asymmetric chromosome segregation and cell division in DNA damage-induced bacterial filaments

2020 ◽  
Vol 31 (26) ◽  
pp. 2920-2931
Author(s):  
Suchitha Raghunathan ◽  
Afroze Chimthanawala ◽  
Sandeep Krishna ◽  
Anthony G. Vecchiarelli ◽  
Anjana Badrinarayanan
Keyword(s):  
Dna Damage ◽  
Cell Division ◽  
Dna Damage Response ◽  
Chromosome Segregation ◽  
Asymmetric Division ◽  
Model Systems ◽  
Wild Type ◽  
Central Function ◽  
Damage Response ◽  
Bacterial Model

The DNA damage response and cell division checkpoints have been well studied in several bacterial model systems, but how cells exit such a checkpoint to restart wild-type growth is unclear. This study highlights a central function for asymmetric division in mediating cellular recovery from DNA damage.

scholarly journals Pericentromere tension is self-regulated by spindle structure in metaphase

2014 ◽  
Vol 205 (3) ◽  
pp. 313-324 ◽  
Author(s):  
Jeremy M. Chacón ◽  
Soumya Mukherjee ◽  
Breanna M. Schuster ◽  
Duncan J. Clarke ◽  
Melissa K. Gardner
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Division ◽  
Chromosome Segregation ◽  
Mitotic Spindle ◽  
Chromosome Structure ◽  
Wild Type ◽  
Checkpoint Signaling ◽  
Daughter Cells ◽  
Fluorescent Markers ◽  
Spindle Structure

During cell division, a mitotic spindle is built by the cell and acts to align and stretch duplicated sister chromosomes before their ultimate segregation into daughter cells. Stretching of the pericentromeric chromatin during metaphase is thought to generate a tension-based signal that promotes proper chromosome segregation. However, it is not known whether the mitotic spindle actively maintains a set point tension magnitude for properly attached sister chromosomes to facilitate robust mechanochemical checkpoint signaling. By imaging and tracking the thermal movements of pericentromeric fluorescent markers in Saccharomyces cerevisiae, we measured pericentromere stiffness and then used the stiffness measurements to quantitatively evaluate the tension generated by pericentromere stretch during metaphase in wild-type cells and in mutants with disrupted chromosome structure. We found that pericentromere tension in yeast is substantial (4–6 pN) and is tightly self-regulated by the mitotic spindle: through adjustments in spindle structure, the cell maintains wild-type tension magnitudes even when pericentromere stiffness is disrupted.

scholarly journals Mitotic Spindle Positioning in Saccharomyces cerevisiae Is Accomplished by Antagonistically Acting Microtubule Motor Proteins

1997 ◽  
Vol 138 (5) ◽  
pp. 1041-1053 ◽  
Author(s):  
Frank R. Cottingham ◽  
M. Andrew Hoyt
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Division ◽  
Mitotic Spindle ◽  
Asymmetric Cell Division ◽  
Wild Type ◽  
Yeast Saccharomyces Cerevisiae ◽  
Spindle Positioning ◽  
Dynein Motor ◽  
Bud Neck ◽  
Microtubule Motor

Proper positioning of the mitotic spindle is often essential for cell division and differentiation processes. The asymmetric cell division characteristic of budding yeast, Saccharomyces cerevisiae, requires that the spindle be positioned at the mother–bud neck and oriented along the mother–bud axis. The single dynein motor encoded by the S. cerevisiae genome performs an important but nonessential spindle-positioning role. We demonstrate that kinesin-related Kip3p makes a major contribution to spindle positioning in the absence of dynein. The elimination of Kip3p function in dyn1Δ cells severely compromised spindle movement to the mother–bud neck. In dyn1Δ cells that had completed positioning, elimination of Kip3p function caused spindles to mislocalize to distal positions in mother cell bodies. We also demonstrate that the spindle-positioning defects exhibited by dyn1 kip3 cells are caused, to a large extent, by the actions of kinesin- related Kip2p. Microtubules in kip2Δ cells were shorter and more sensitive to benomyl than wild-type, in contrast to the longer and benomyl-resistant microtubules found in dyn1Δ and kip3Δ cells. Most significantly, the deletion of KIP2 greatly suppressed the spindle localization defect and slow growth exhibited by dyn1 kip3 cells. Likewise, induced expression of KIP2 caused spindles to mislocalize in cells deficient for dynein and Kip3p. Our findings indicate that Kip2p participates in normal spindle positioning but antagonizes a positioning mechanism acting in dyn1 kip3 cells. The observation that deletion of KIP2 could also suppress the inviability of dyn1Δ kar3Δ cells suggests that kinesin-related Kar3p also contributes to spindle positioning.

scholarly journals Cell division requires RNA eviction from condensing chromosomes

2020 ◽  
Vol 219 (11) ◽  
Author(s):  
Judith A. Sharp ◽  
Carlos Perea-Resa ◽  
Wei Wang ◽  
Michael D. Blower
Keyword(s):  
Cell Division ◽  
Chromosome Segregation ◽  
Mitotic Chromosome ◽  
Aurora B ◽  
Nucleic Acid Binding ◽  
Mitotic Chromosomes ◽  
Nuclear Envelope Breakdown ◽  
Binding Domains ◽  
Chromosome Alignment ◽  
Rna Complexes

During mitosis, the genome is transformed from a decondensed, transcriptionally active state to a highly condensed, transcriptionally inactive state. Mitotic chromosome reorganization is marked by the general attenuation of transcription on chromosome arms, yet how the cell regulates nuclear and chromatin-associated RNAs after chromosome condensation and nuclear envelope breakdown is unknown. SAF-A/hnRNPU is an abundant nuclear protein with RNA-to-DNA tethering activity, coordinated by two spatially distinct nucleic acid–binding domains. Here we show that RNA is evicted from prophase chromosomes through Aurora-B–dependent phosphorylation of the SAF-A DNA-binding domain; failure to execute this pathway leads to accumulation of SAF-A–RNA complexes on mitotic chromosomes, defects in metaphase chromosome alignment, and elevated rates of chromosome missegregation in anaphase. This work reveals a role for Aurora-B in removing chromatin-associated RNAs during prophase and demonstrates that Aurora-B–dependent relocalization of SAF-A during cell division contributes to the fidelity of chromosome segregation.

Interallelic Complementation at the suppressor of forked Locus of Drosophila Reveals Complementation Between Suppressor of forked Proteins Mutated in Different Regions

Genetics ◽  
1996 ◽  
Vol 142 (4) ◽  
pp. 1225-1235
Author(s):  
Martine Simonelig ◽  
Kate Elliott ◽  
Andrew Mitchelson ◽  
Kevin O'Hare
Keyword(s):  
Drosophila Melanogaster ◽  
Gene Product ◽  
Protein Interaction ◽  
Wild Type ◽  
Type Function ◽  
Protein Protein Interaction ◽  
Molecular Complexity ◽  
Interallelic Complementation ◽  
Cleavage Stimulation Factor ◽  
Different Parts

Abstract The Su(f) protein of Drosophila melanogaster shares extensive homologies with proteins from yeast (RNA14) and man (77 kD subunit of cleavage stimulation factor) that are required for 3′ end processing of mRNA. These homologies suggest that su(f) is involved in mRNA 3′ end formation and that some aspects of this process are conserved throughout eukaryotes. We have investigated the genetic and molecular complexity of the su(f) locus. The su(f) gene is transcribed to produce three RNAs and could encode two proteins. Using constructs that contain different parts of the locus, we show that only the larger predicted gene product of 84 kD is required for the wild-type function of su(f). Some lethal alleles of su(f) complement to produce viable combinations. The structures of complementing and noncomplementing su(f) alleles indicate that 84-kD Su(f) proteins mutated in different domains can act in combination for partial su(f) function. Our results suggest protein-protein interaction between or within wild-type Su(f) molecules.

scholarly journals DUSP7 Regulates the Activity of ERK2 to Promote Proper Chromosome Alignment During Cell Division

2020 ◽  
Author(s):  
Xiao Guo ◽  
Yenni A. Garcia ◽  
Ivan Ramirez ◽  
Erick F. Velasquez ◽  
Lucy W. Gao ◽  
...  
Keyword(s):  
Cell Division ◽  
Chromosome Segregation ◽  
Human Cell ◽  
Mitotic Chromosome ◽  
Marked Decrease ◽  
Metaphase Plate ◽  
Chromosome Congression ◽  
Dual Specificity ◽  
Chromosome Alignment ◽  
Chemical Inhibition

SUMMARYHuman cell division is a highly regulated process that relies on the accurate capture and movement of chromosomes to the metaphase plate. Errors in the fidelity of chromosome congression and alignment can lead to improper chromosome segregation, which is correlated with aneuploidy and tumorigenesis. Here we show that the dual specificity phosphatase DUSP7 is important for regulating chromosome alignment. DUSP7 bound to ERK2 and regulated the abundance of active phospho-ERK2 through its phosphatase activity. Overexpression of DUSP7, but not catalytic dead mutants, led to a marked decrease in phopho-ERK2 and mitotic chromosome misalignment, while knockdown of DUSP7 also led to defective chromosome congression that resulted in a prolonged mitosis. Consistently, chemical inhibition of the MEK kinase that phosphorylates ERK2 or ERK2 itself led to chromosome alignment defects. Our results support a model where MEK phosphorylation and DUSP7 dephosphorylation regulate the levels of active phospho-ERK2 to promote proper cell division.

scholarly journals Nonrecombinant meiosis I nondisjunction in Saccharomyces cerevisiae induced by tRNA ochre suppressors.

Genetics ◽  
1989 ◽  
Vol 123 (1) ◽  
pp. 81-95 ◽  
Author(s):  
E J Louis ◽  
J E Haber
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Mitotic Chromosome ◽  
Stop Codon ◽  
Fold Increase ◽  
Wild Type ◽  
Yeast Saccharomyces Cerevisiae ◽  
Nonsense Mutations ◽  
Chromosome Iii ◽  
Meiosis I ◽  
Chromosome Nondisjunction

Abstract The presence of the tRNA ochre suppressors SUP11 and SUP5 is found to induce meiosis I nondisjunction in the yeast Saccharomyces cerevisiae. The induction increases with increasing dosage of the suppressor and decreases in the presence of an antisuppressor. The effect is independent of the chromosomal location of SUP11. Each of five different chromosomes monitored exhibited nondisjunction at frequencies of 0.1%-1.1% of random spores, which is a 16-160-fold increase over wild-type levels. Increased nondisjunction is reflected by a marked increase in tetrads with two and zero viable spores. In the case of chromosome III, for which a 50-cM map interval was monitored, the resulting disomes are all in the parental nonrecombinant configuration. Recombination along chromosome III appears normal both in meioses that have no nondisjunction and in meioses for which there was nondisjunction of another chromosome. We propose that a proportion of one or more proteins involved in chromosome pairing, recombination or segregation are aberrant due to translational read-through of the normal ochre stop codon. Hygromycin B, an antibiotic that can suppress nonsense mutations via translational read-through, also induces nonrecombinant meiosis I nondisjunction. Increases in mistranslation, therefore, increase the production of aneuploids during meiosis. There was no observable effect of SUP11 on mitotic chromosome nondisjunction; however some disomes caused SUP11 ade2-ochre strains to appear white or red, instead of pink.

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