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Related Concept Videos

Forces Acting on Chromosomes02:11

Forces Acting on Chromosomes

During mitosis, chromosome movements occur through the interplay of multiple piconewton level forces. In prometaphase, these forces help in chromosome assembly or congression at the equatorial plane, eventually leading to their alignment at the metaphase plate. The forces acting on the chromosomes are space and time-dependent; therefore, they vary with the position of the chromosomes as the cell progresses through mitosis. 
Microtubules and motor proteins exert two types of forces on...
Forces Acting on Chromosomes02:11

Forces Acting on Chromosomes

During mitosis, chromosome movements occur through the interplay of multiple piconewton level forces. In prometaphase, these forces help in chromosome assembly or congression at the equatorial plane, eventually leading to their alignment at the metaphase plate. The forces acting on the chromosomes are space and time-dependent; therefore, they vary with the position of the chromosomes as the cell progresses through mitosis. 
Microtubules and motor proteins exert two types of forces on...
Attachment of Sister Chromatids02:57

Attachment of Sister Chromatids

As cells progress into mitosis, the nuclear envelope breaks down, and the condensed chromosomes are exposed to the array of bipolar microtubules of the mitotic spindle. The kinetochore, a large, disc-shaped protein complex, is present at the centromere region of the sister chromatids and acts as a binding site for the microtubules.  Usually, the plus-end of a single microtubule is embedded within the kinetochore. However, some kinetochores first establish lateral contact with the side-wall of a...
Chromosome Structure02:40

Chromosome Structure

A functional eukaryotic chromosome must contain three elements: a centromere, telomeres, and numerous origins of replication.
The centromere is a DNA sequence that links sister chromatids. This is also where kinetochores, protein complexes to which spindle microtubules attach, are constructed after the chromosome is replicated. The kinetochores allow the spindle microtubules to move the chromosomes within the cell during cell division.
Telomeres consist of non-coding repetitive nucleotide...
Chromosome Structure02:40

Chromosome Structure

A functional eukaryotic chromosome must contain three elements: a centromere, telomeres, and numerous origins of replication.
The centromere is a DNA sequence that links sister chromatids. This is also where kinetochores, protein complexes to which spindle microtubules attach, are constructed after the chromosome is replicated. The kinetochores allow the spindle microtubules to move the chromosomes within the cell during cell division.
Telomeres consist of non-coding repetitive nucleotide...
Anaphase A and B01:39

Anaphase A and B

Microtubules form through the end-to-end polymerization of tubulin heterodimers. Kinetochore microtubules originate from the spindle poles, and their plus-ends connect with the kinetochores on sister-chromatids. Ndc80 protein complexes, present on the kinetochore, form low-affinity links with the plus end of these kinetochore microtubules.
Plus-end depolymerization releases tubulin heterodimers from the terminal region of the microtubule. As tubulin subunits are lost, the Ndc80 complexes detach...

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Associated Chromosome Trap for Identifying Long-range DNA Interactions
14:49

Associated Chromosome Trap for Identifying Long-range DNA Interactions

Published on: April 23, 2011

Dynamical scenarios for chromosome bi-orientation.

Tongli Zhang1, Raquel A Oliveira, Bernhard Schmierer

  • 1Oxford Centre for Integrative Systems Biology, Department of Biochemistry, University of Oxford, Oxford, United Kingdom.

Biophysical Journal
|June 25, 2013
PubMed
Summary

Chromosome bi-orientation is essential for accurate cell division. This process is error-prone, and cells use mechanisms to correct misaligned chromosomes. The study explores how cells might achieve bi-orientation from unattached kinetochores. Tension between sister kinetochores creates a bistable switch, but this mechanism alone does not explain the initial steps. The researchers propose four possible mechanisms to address this issue. They find that trial-and-error oscillation and stochastic bistable switches are effective in promoting bi-orientation. These mechanisms are supported by experimental data. The study does not claim these are the only possible solutions but highlights their potential for efficiency and robustness.

Keywords:
cell divisionkinetochore attachmentspindle dynamicserror correction

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Area of Science:

  • Cell biology
  • Molecular genetics
  • Chromosome dynamics

Background:

Chromosome segregation during cell division requires accurate bi-orientation. This process is inherently error-prone. Existing mechanisms help correct misaligned chromosomes. Prior research has shown that tension between sister kinetochores influences attachment stability. However, the initial steps of bi-orientation remain unclear. No prior work had resolved how unattached kinetochores transition to bi-orientation. This gap motivated the investigation of possible dynamical scenarios. The study aims to identify mechanisms that could support both efficiency and robustness in bi-orientation.

Purpose Of The Study:

The goal is to explore how cells achieve chromosome bi-orientation. The study focuses on error-prone processes and correction mechanisms. It examines tension-mediated feedback between sister kinetochores. The researchers aim to understand how bi-orientation initiates from unattached kinetochores. Four possible mechanisms are proposed to address this challenge. The study evaluates the impact of each mechanism on bi-orientation. Experimental data supports the assessment of these scenarios. The purpose is to identify robust and efficient pathways for bi-orientation.

Main Methods:

The researchers analyzed several dynamical scenarios for bi-orientation. They first modeled tension-mediated feedback between sister kinetochores. This feedback was shown to create a bistable switch. The model distinguishes between low and high tension states. However, the model fails to explain initial attachment from unattached kinetochores. The team proposed four alternative mechanisms to address this issue. These include molecular noise, tension-independent attachment, trial-and-error oscillation, and stochastic bistable switches. The impact of each mechanism on bi-orientation was assessed using simulations and experimental data.

Main Results:

Tension-mediated feedback leads to a bistable switch between low and high tension. This mechanism supports robust distinction between attachment states. However, it does not explain how bi-orientation initiates from unattached kinetochores. The researchers evaluated four proposed mechanisms for this process. Molecular noise and tension-independent attachment were considered. Trial-and-error oscillation and stochastic bistable switches were also tested. The trial-and-error oscillation showed potential for efficient bi-orientation. The stochastic bistable switch also supported robust and efficient bi-orientation. Experimental data supported the effectiveness of these two mechanisms.

Conclusions:

The study concludes that trial-and-error oscillation and stochastic bistable switches are effective. These mechanisms support both efficiency and robustness in bi-orientation. The researchers propose that these mechanisms may explain how cells initiate bi-orientation. The findings are supported by experimental data. The study does not claim that these are the only possible mechanisms. Other proposed mechanisms were less effective in simulations. The conclusions are limited to the scenarios tested in the study. The authors suggest further investigation of these mechanisms in live cells.

The study proposes trial-and-error oscillation and stochastic bistable switches as core mechanisms.

Tension-mediated feedback creates a bistable switch between low and high tension states.

Tension-independent attachment allows kinetochores to bind before tension is established.

Molecular noise may help kinetochores escape from incorrect attachment states.

Trial-and-error oscillations test different configurations until bi-orientation is achieved.

The authors suggest these switches promote both efficient and robust bi-orientation.