scholarly journals Mitotic chromosome length scales in response to both cell and nuclear size

2015 ◽  
Vol 209 (5) ◽  
pp. 645-652 ◽  
Author(s):  
Anne-Marie Ladouceur ◽  
Jonas F. Dorn ◽  
Paul S. Maddox
Keyword(s):  
Cell Size ◽  
Chromosome Segregation ◽  
Mitotic Spindle ◽  
Mitotic Chromosome ◽  
Time Lapse ◽  
Chromosome Length ◽  
Nuclear Size ◽  
Multicellular Development ◽  
Length Regulation ◽  
Cellular Integrity

Multicellular development requires that cells reduce in size as a result of consecutive cell divisions without increase in embryo volume. To maintain cellular integrity, organelle size adapts to cell size throughout development. During mitosis, the longest chromosome arm must be shorter than half of the mitotic spindle for proper chromosome segregation. Using high-resolution time-lapse microscopy of living Caenorhabditis elegans embryos, we have quantified the relation between cell size and chromosome length. In control embryos, chromosome length scaled to cell size. Artificial reduction of cell size resulted in a shortening of chromosome length, following a trend predicted by measurements from control embryos. Disturbing the RAN (Ras-related nuclear protein)-GTP gradient decoupled nuclear size from cell size and resulted in chromosome scaling to nuclear size rather than cell size; smaller nuclei contained shorter chromosomes independent of cell size. In sum, quantitative analysis relating cell, nuclear, and chromosome size predicts two levels of chromosome length regulation: one through cell size and a second in response to nuclear size.

scholarly journals The budding yeast Ipl1/Aurora protein kinase regulates mitotic spindle disassembly

2003 ◽  
Vol 160 (3) ◽  
pp. 329-339 ◽  
Author(s):  
Stéphanie Buvelot ◽  
Sean Y. Tatsutani ◽  
Danielle Vermaak ◽  
Sue Biggins
Keyword(s):  
Chromosome Segregation ◽  
Mitotic Spindle ◽  
Kinase Activity ◽  
Budding Yeast ◽  
Genomic Stability ◽  
Time Lapse ◽  
Time Lapse Microscopy ◽  
Spindle Disassembly ◽  
Spindle Midzone ◽  
Spindle Microtubules

Ipl1p is the budding yeast member of the Aurora family of protein kinases, critical regulators of genomic stability that are required for chromosome segregation, the spindle checkpoint, and cytokinesis. Using time-lapse microscopy, we found that Ipl1p also has a function in mitotic spindle disassembly that is separable from its previously identified roles. Ipl1–GFP localizes to kinetochores from G1 to metaphase, transfers to the spindle after metaphase, and accumulates at the spindle midzone late in anaphase. Ipl1p kinase activity increases at anaphase, and ipl1 mutants can stabilize fragile spindles. As the spindle disassembles, Ipl1p follows the plus ends of the depolymerizing spindle microtubules. Many Ipl1p substrates colocalize with Ipl1p to the spindle midzone, identifying additional proteins that may regulate spindle disassembly. We propose that Ipl1p regulates both the kinetochore and interpolar microtubule plus ends to regulate its various mitotic functions.

scholarly journals Emerging Insights into the Function of Kinesin-8 Proteins in Microtubule Length Regulation

2018 ◽  
Author(s):  
Sanjay Shrestha ◽  
Mark Hazelbaker ◽  
Amber L. Yount ◽  
Claire E. Walczak
Keyword(s):  
Motor Activity ◽  
Chromosome Segregation ◽  
Mitotic Spindle ◽  
Structure And Function ◽  
Cellular Processes ◽  
Cellular Factors ◽  
Destabilizing Factors ◽  
Length Regulation ◽  
Mitotic Spindle Assembly ◽  
And Function

Proper regulation of microtubules (MTs) is critical for the execution of diverse cellular processes, including mitotic spindle assembly and chromosome segregation. There are a multitude of cellular factors that regulate the dynamicity of MTs and play critical roles in mitosis. Members of the Kinesin-8 family of motor proteins act as MT-destabilizing factors to control MT length in a spatially and temporally regulated manner. In this review, we focus on recent advances in our understanding of the structure and function of the Kinesin-8 motor domain, and the emerging contributions of the C-terminal tail of Kinesin-8 proteins to regulate motor activity and localization.

Chromosome length controls mitotic chromosome segregation in yeast

Cell ◽  
1986 ◽  
Vol 45 (4) ◽  
pp. 529-536 ◽  
Author(s):  
Andrew W. Murray ◽  
Neil P. Schultes ◽  
Jack W. Szostak
Keyword(s):  
Chromosome Segregation ◽  
Mitotic Chromosome ◽  
Chromosome Length

scholarly journals Emerging Insights into the Function of Kinesin-8 Proteins in Microtubule Length Regulation

Biomolecules ◽  
2018 ◽  
Vol 9 (1) ◽  
pp. 1 ◽  
Author(s):  
Sanjay Shrestha ◽  
Mark Hazelbaker ◽  
Amber Yount ◽  
Claire Walczak
Keyword(s):  
Motor Activity ◽  
Chromosome Segregation ◽  
Mitotic Spindle ◽  
Structure And Function ◽  
Cellular Processes ◽  
Cellular Factors ◽  
Destabilizing Factors ◽  
Length Regulation ◽  
Mitotic Spindle Assembly ◽  
And Function

Proper regulation of microtubules (MTs) is critical for the execution of diverse cellular processes, including mitotic spindle assembly and chromosome segregation. There are a multitude of cellular factors that regulate the dynamicity of MTs and play critical roles in mitosis. Members of the Kinesin-8 family of motor proteins act as MT-destabilizing factors to control MT length in a spatially and temporally regulated manner. In this review, we focus on recent advances in our understanding of the structure and function of the Kinesin-8 motor domain, and the emerging contributions of the C-terminal tail of Kinesin-8 proteins to regulate motor activity and localization.

The role of the cortical cytoskeleton: F-actin crosslinking proteins protect against osmotic stress, ensure cell size, cell shape and motility, and contribute to phagocytosis and development

1996 ◽  
Vol 109 (11) ◽  
pp. 2679-2691 ◽  
Author(s):  
F. Rivero ◽  
B. Koppel ◽  
B. Peracino ◽  
S. Bozzaro ◽  
F. Siegert ◽  
...  
Keyword(s):  
Osmotic Stress ◽  
Cell Size ◽  
Cell Shape ◽  
Developmental Stages ◽  
Osmotic Shock ◽  
Time Lapse ◽  
Wild Type ◽  
Protective Function ◽  
Multicellular Development ◽  
Mutant Cells

We generated Dictyostelium double mutants lacking the two F-actin crosslinking proteins alpha-actinin and gelation factor by inactivating the corresponding genes via homologous recombination. Here we investigated the consequences of these deficiencies both at the single cell level and at the multicellular stage. We found that loss of both proteins severely affected growth of the mutant cells in shaking suspension, and led to a reduction of cell size from 12 microns in wild-type cells to 9 microns in mutant cells. Moreover the cells did not exhibit the typical polarized morphology of aggregating Dictyostelium cells but had a more rounded cell shape, and also exhibited an increased sensitivity towards osmotic shock and a reduced rate of phagocytosis. Development was heavily impaired and never resulted in the formation of fruiting bodies. Expression of developmentally regulated genes and the final developmental stages that were reached varied, however, with the substrata on which the cells were deposited. On phosphate buffered agar plates the cells were able to form tight aggregates and mounds and to express prespore and prestalk cell specific genes. Under these conditions the cells could perform chemotactic signalling and cell behavior was normal at the onset of multicellular development as revealed by time-lapse video microscopy. Double mutant cells were motile but speed was reduced by approximately 30% as compared to wild type. These changes were reversed by expressing the gelation factor in the mutant cells. We conclude that the actin assemblies that are formed and/or stabilized by both F-actin crosslinking proteins have a protective function during osmotic stress and are essential for proper cell shape and motility.

scholarly journals A mitotic SKAP isoform regulates spindle positioning at astral microtubule plus ends

2016 ◽  
Vol 213 (3) ◽  
pp. 315-328 ◽  
Author(s):  
David M. Kern ◽  
Peter K. Nicholls ◽  
David C. Page ◽  
Iain M. Cheeseman
Keyword(s):  
Chromosome Segregation ◽  
Mitotic Spindle ◽  
Mitotic Chromosome ◽  
Cell Cortex ◽  
Microtubule Binding ◽  
Spindle Positioning ◽  
Astral Microtubule ◽  
Chromosome Alignment ◽  
Pulling Forces ◽  
Mitotic Cells

The Astrin/SKAP complex plays important roles in mitotic chromosome alignment and centrosome integrity, but previous work found conflicting results for SKAP function. Here, we demonstrate that SKAP is expressed as two distinct isoforms in mammals: a longer, testis-specific isoform that was used for the previous studies in mitotic cells and a novel, shorter mitotic isoform. Unlike the long isoform, short SKAP rescues SKAP depletion in mitosis and displays robust microtubule plus-end tracking, including localization to astral microtubules. Eliminating SKAP microtubule binding results in severe chromosome segregation defects. In contrast, SKAP mutants specifically defective for plus-end tracking facilitate proper chromosome segregation but display spindle positioning defects. Cells lacking SKAP plus-end tracking have reduced Clasp1 localization at microtubule plus ends and display increased lateral microtubule contacts with the cell cortex, which we propose results in unbalanced dynein-dependent cortical pulling forces. Our work reveals an unappreciated role for the Astrin/SKAP complex as an astral microtubule mediator of mitotic spindle positioning.

scholarly journals Genes Involved in Sister Chromatid Separation and Segregation in the Budding Yeast Saccharomyces cerevisiae

Genetics ◽  
2001 ◽  
Vol 159 (2) ◽  
pp. 453-470
Author(s):  
Sue Biggins ◽  
Needhi Bhalla ◽  
Amy Chang ◽  
Dana L Smith ◽  
Andrew W Murray
Keyword(s):  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Mitotic Spindle ◽  
Budding Yeast ◽  
Temperature Sensitive ◽  
Chromosome Behavior ◽  
Yeast Saccharomyces Cerevisiae ◽  
Sister Chromatids ◽  
Marked Chromosome ◽  
Sister Chromatid Separation

Abstract Accurate chromosome segregation requires the precise coordination of events during the cell cycle. Replicated sister chromatids are held together while they are properly attached to and aligned by the mitotic spindle at metaphase. At anaphase, the links between sisters must be promptly dissolved to allow the mitotic spindle to rapidly separate them to opposite poles. To isolate genes involved in chromosome behavior during mitosis, we microscopically screened a temperature-sensitive collection of budding yeast mutants that contain a GFP-marked chromosome. Nine LOC (loss of cohesion) complementation groups that do not segregate sister chromatids at anaphase were identified. We cloned the corresponding genes and performed secondary tests to determine their function in chromosome behavior. We determined that three LOC genes, PDS1, ESP1, and YCS4, are required for sister chromatid separation and three other LOC genes, CSE4, IPL1, and SMT3, are required for chromosome segregation. We isolated alleles of two genes involved in splicing, PRP16 and PRP19, which impair α-tubulin synthesis thus preventing spindle assembly, as well as an allele of CDC7 that is defective in DNA replication. We also report an initial characterization of phenotypes associated with the SMT3/SUMO gene and the isolation of WSS1, a high-copy smt3 suppressor.

scholarly journals Targeting the Process of Mitotic Chromosome Segregation as a Novel Sensitizing Target to Radiation Treatment

2015 ◽  
Vol 93 (3) ◽  
pp. S50
Author(s):  
A. Laughney ◽  
J. Murnane ◽  
G. Genovese ◽  
S. Elizalde ◽  
D. Compton ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Mitotic Chromosome ◽  
Radiation Treatment

scholarly journals Monitoring the fidelity of mitotic chromosome segregation by the spindle assembly checkpoint

2011 ◽  
Vol 44 (5) ◽  
pp. 391-400 ◽  
Author(s):  
P. Silva ◽  
J. Barbosa ◽  
A. V. Nascimento ◽  
J. Faria ◽  
R. Reis ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Spindle Assembly Checkpoint ◽  
Mitotic Chromosome ◽  
Spindle Assembly

CSE1 and CSE2, two new genes required for accurate mitotic chromosome segregation in Saccharomyces cerevisiae

1993 ◽  
Vol 13 (8) ◽  
pp. 4691-4702 ◽  
Author(s):  
Z Xiao ◽  
J T McGrew ◽  
A J Schroeder ◽  
M Fitzgerald-Hayes
Keyword(s):  
Chromosome Segregation ◽  
Leucine Zipper ◽  
Mitotic Chromosome ◽  
Restrictive Temperature ◽  
Permissive Temperature ◽  
New Genes ◽  
Marked Chromosome ◽  
Cold Sensitive ◽  
Basic Region ◽  
Segregation Of Chromosomes

By monitoring the mitotic transmission of a marked chromosome bearing a defective centromere, we have identified conditional alleles of two genes involved in chromosome segregation (cse). Mutations in CSE1 and CSE2 have a greater effect on the segregation of chromosomes carrying mutant centromeres than on the segregation of chromosomes with wild-type centromeres. In addition, the cse mutations cause predominantly nondisjunction rather than loss events but do not cause a detectable increase in mitotic recombination. At the restrictive temperature, cse1 and cse2 mutants accumulate large-budded cells, with a significant fraction exhibiting aberrant binucleate morphologies. We cloned the CSE1 and CSE2 genes by complementation of the cold-sensitive phenotypes. Physical and genetic mapping data indicate that CSE1 is linked to HAP2 on the left arm of chromosome VII and CSE2 is adjacent to PRP2 on chromosome XIV. CSE1 is essential and encodes a novel 109-kDa protein. CSE2 encodes a 17-kDa protein with a putative basic-region leucine zipper motif. Disruption of CSE2 causes chromosome missegregation, conditional lethality, and slow growth at the permissive temperature.

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