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Questions and Answers
What is essential for proper chromosome segregation during cell division?
What is essential for proper chromosome segregation during cell division?
What role do outer kinetochore proteins play in the attachment of microtubules?
What role do outer kinetochore proteins play in the attachment of microtubules?
Which process is driven by the depolymerization of microtubule plus ends at the kinetochore?
Which process is driven by the depolymerization of microtubule plus ends at the kinetochore?
What happens to sister chromatids after cohesin is removed?
What happens to sister chromatids after cohesin is removed?
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How does dynein contribute to the separation of spindle poles during Anaphase B?
How does dynein contribute to the separation of spindle poles during Anaphase B?
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During which phase does the spindle elongate, further separating chromosomes?
During which phase does the spindle elongate, further separating chromosomes?
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What is the primary reason chromosomes can stay attached even as microtubules grow and shrink?
What is the primary reason chromosomes can stay attached even as microtubules grow and shrink?
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What initiates the separation of sister chromatids during cell division?
What initiates the separation of sister chromatids during cell division?
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Which statement accurately describes the behavior of kinetochores during chromosome oscillation?
Which statement accurately describes the behavior of kinetochores during chromosome oscillation?
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What happens during the S phase of the cell cycle?
What happens during the S phase of the cell cycle?
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What is the role of the cohesin complex during mitosis?
What is the role of the cohesin complex during mitosis?
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What event occurs during prophase of mitosis?
What event occurs during prophase of mitosis?
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During which phase do chromosomes align at the metaphase plate?
During which phase do chromosomes align at the metaphase plate?
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Which statement correctly describes spindle assembly?
Which statement correctly describes spindle assembly?
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What is the significance of chromosome condensation during mitosis?
What is the significance of chromosome condensation during mitosis?
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What characterizes the state of sister chromatids after S phase?
What characterizes the state of sister chromatids after S phase?
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Which structure forms at the center of the cell during telophase?
Which structure forms at the center of the cell during telophase?
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Which of the following structures is involved in the dynamic movement of chromosomes?
Which of the following structures is involved in the dynamic movement of chromosomes?
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What occurs during cytokinesis?
What occurs during cytokinesis?
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How many stages comprise the process of mitosis?
How many stages comprise the process of mitosis?
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In which phase is the nuclear envelope reformed?
In which phase is the nuclear envelope reformed?
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What happens to chromosomes during anaphase?
What happens to chromosomes during anaphase?
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What is the primary purpose of mitotic spindle in cell division?
What is the primary purpose of mitotic spindle in cell division?
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What role do condensins play in chromosome organization during mitosis?
What role do condensins play in chromosome organization during mitosis?
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What is the primary function of kinesin-5 during spindle assembly?
What is the primary function of kinesin-5 during spindle assembly?
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How does the dynamic instability of microtubules in mitosis contribute to chromosome alignment?
How does the dynamic instability of microtubules in mitosis contribute to chromosome alignment?
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Which component organizes microtubules into a bipolar spindle during mitosis?
Which component organizes microtubules into a bipolar spindle during mitosis?
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What is the role of kinetochores during the 'search and capture' process?
What is the role of kinetochores during the 'search and capture' process?
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What is the effect of increased catastrophe frequency of microtubules during mitosis?
What is the effect of increased catastrophe frequency of microtubules during mitosis?
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Which structural component is crucial for the formation of stable kinetochore-microtubule attachments?
Which structural component is crucial for the formation of stable kinetochore-microtubule attachments?
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Which statement correctly describes the positioning of sister chromatids during metaphase?
Which statement correctly describes the positioning of sister chromatids during metaphase?
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What happens to microtubules in the mitotic spindle as the cell enters anaphase?
What happens to microtubules in the mitotic spindle as the cell enters anaphase?
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What is primarily responsible for the movement of chromosomes during mitosis?
What is primarily responsible for the movement of chromosomes during mitosis?
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Which of the following statements is true about sister chromatids?
Which of the following statements is true about sister chromatids?
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During which phase do chromosomes first become distinctly visualized?
During which phase do chromosomes first become distinctly visualized?
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What is an essential characteristic of microtubules during the M phase?
What is an essential characteristic of microtubules during the M phase?
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How does the breakdown of the nuclear envelope influence microtubule function?
How does the breakdown of the nuclear envelope influence microtubule function?
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Study Notes
Chromosome Segregation
- Chromosomes must be bioriented to segregate properly
- Biorientation creates tension on the kinetochores, allowing the cell to monitor attachments
- Microtubules remain dynamic and chromosomes oscillate even after biorientation
- Outer kinetochore proteins bind to the sides of microtubules, allowing microtubules to dynamically grow and shrink without detaching from kinetochore
Cohesin Removal and Separase
- For sister chromatids to seperate, cohesin must be removed
- Separase is the protein that cleaves cohesin rings
Anaphase
- Two mechanisms drive chromosome segregation during anaphase: Anaphase A and Anaphase B
- Anaphase A: chromosomes move to spindle poles driven by microtubule depolymerization at kinetochore
- Anaphase B: spindle poles separate driven by kinesin-5 and dynein
Dynein Activity in Anaphase B
- Astral microtubules extend towards the cell cortex
- Dynein at the cell cortex walks towards the minus ends of astral microtubules
- This generates a pulling force that reels in the astral microtubule and pulls the centrosome closer to the plasma membrane
Interphase vs. Mitosis Chromosomes
- Individual chromosomes are visible in mitosis due to increased condensation.
- It is harder to distinguish individual chromosomes in interphase because they are less condensed.
Condensins in Chromosome Condensation
- Condensins are protein complexes that form rings that function to condense DNA in mitosis.
- They help organize the DNA into loops which results in full condensation of mitotic chromosomes.
Spindle Assembly
- Centrosomes nucleate microtubules
- Centrosomes duplicate during S phase
- Centrosomes separate along the outside of the nuclear envelope
- A bipolar spindle forms with a centrosome at each pole nucleating microtubules
- The nuclear envelope breaks down to allow microtubules to capture chromosomes
Microtubule Dynamic Instability
- Microtubules undergo phases of growth and shrinkage by addition/loss of tubulin subunits
- Dynamic instability increases in mitosis compared to interphase
- This increased dynamics facilitates breakdown and rearrangement of the interphase microtubule array and attachment of chromosomes to the spindle
Microtubule Dynamics in the Mitotic Spindle
- While microtubules are dynamic in mitosis, specific populations are stabilized.
- Microtubules growing out of the centrosome are highly dynamic and form asters; these are astral microtubules.
- Some astral microtubules become stabilized by cross-linking proteins and become interpolar microtubules.
- Interpolar microtubules help form the football shape of the spindle
- The overlap zone between interpolar microtubules is where kinesin-5 walks to generate outward force.
Kinesin-5 in Spindle Assembly
- Kinesin-5 is a tetrameric kinesin with two heads on each side.
- Both sets of heads can walk to MT plus ends.
- Each set of heads associates with a different microtubule.
Kinesin-5 Function in Spindle Assembly
- Kinesin-5 localizes to the overlap zone of interpolar microtubules.
- It walks towards the plus end of each antiparallel microtubule.
- This outward force pushes the poles apart, promoting centrosome separation during spindle assembly.
Chromosome Capture and Alignment
- After spindle formation, chromosomes begin attaching to microtubules.
- After attachment, captured chromosomes are moved to the middle of the cell, called chromosome congression
Kinetochore Organization
- Kinetochores are protein structures that mediate attachment of microtubules to the centromere.
- Multiple microtubules attach to each kinetochore.
Kinetochore Structure
- Core kinetochore proteins form a platform on the centromere region.
- Outer kinetochore proteins extend and bind to the microtubules.
Search and Capture Process
- Microtubules emanating from centrosomes grow and shrink.
- When a microtubule hits a kinetochore it forms an attachment, known as microtubule capture.
- Eventually, chromosomes become bioriented, with one sister attached to each spindle pole.
Biorientation of Sister Chromatids
- Both sister chromatids must be attached to opposite spindle poles.
M Phase Events
- Chromosome duplication and condensation
- Spindle assembly
- Chromosome capture and alignment
- Chromosome segregation
- Cytokinesis
Chromosome Duplication and Condensation
- DNA duplicates prior to mitosis, resulting in sister chromatids.
- Chromosomes condense to fit the long DNA molecules into the nucleus.
DNA Replication and Sister Chromatids
- Chromosomes duplicate during S phase.
- Sister chromatids are connected by the cohesin complex.
Cohesin Complex
- Cohesin forms a ring around duplicated strands during S phase.
- Responsible for keeping sister chromatids attached until anaphase.
Stages of Mitosis
- Prophase: chromosomes condense, centrosomes move apart.
- Prometaphase: nuclear envelope breaks down, spindle forms, chromosomes captured, chromosome congression.
- Metaphase: chromosomes line up at the metaphase plate.
- Anaphase: sister chromatids move to opposite spindle poles.
- Telophase: contractile ring forms, nuclear envelope reforms.
- Cytokinesis: contractile ring constricts, cell pinches in two, chromosomes decondense.
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