L9: mitosis Flashcards
Why do cells undergo mitosis?
- Reproduction - in single celled organisms
- Growth of multicellular organisms
- Repair or renewal
how does the cell cycle work?
The cell cycle progresses in one direction and is regulated by cellular checkpoints.
G1 Phase – Daughter cells grow, accumulate biomass, and prepare for DNA replication. Once they reach the checkpoint, they enter S phase.
S Phase – DNA is duplicated.
G2 Phase – The cell undergoes net growth, checks if all DNA is properly replicated, and assesses the environment for proliferative factors before proceeding to mitosis.
control of mitosis?
By CDK-cyclin complexes:
CDK (Cyclin-Dependent Kinase) is a kinase that controls the cell cycle.
In simple yeast, the entire cell cycle is regulated by one CDK, but in mammals, M-CDK controls mitosis.
CDK has two subunits:
Catalytic subunit (CDK itself)
Regulatory subunit (Cyclin) – its abundance and activity fluctuate throughout the cycle.
Mitotic cyclin binds to M-CDK and accumulates throughout the cell cycle, reaching its highest concentration just before mitosis.
CDK activation and regulation?
CDK remains inactive for most of G2 due to an inhibitory kinase called Wee1, which adds an inhibitory phosphate to CDK.
CDK is activated by Cdc25, a phosphatase that removes the inhibitory phosphate.
As the cell approaches the G2/M transition, CDK activity rises, triggering:
phosphorylation and Inhibition of Wee1 (stopping further inhibition)
Activation of Cdc25 (enhancing CDK activation)
This creates a positive feedback loop, ensuring a rapid and irreversible transition into mitosis.
mitosis stages?
Prophase
Nuclear envelope begins to disassemble.
Chromosomes condense (shown in red in the image).
Microtubules, which will form the mitotic spindle, are still mostly in the cytosol.
Prometaphase
Microtubules rearrange into the mitotic spindle.
Nuclear envelope fully disassembles.
Microtubules attach to chromosomes at the kinetochores.
Metaphase
Chromosomes align at the equator of the mitotic spindle.
Each chromatid must be correctly attached to the mitotic spindle before progressing.
Anaphase
The connections between sister chromatids are severed.
The mitotic spindle elongates.
Sister chromatids are pulled apart, moving to opposite poles of the cell.
Telophase
Nuclear envelope reforms around each set of chromosomes.
Chromosomes decondense.
Cytokinesis
The cytoplasm divides, completing cell division.
SMC?
SMC (Structural Maintenance of Chromosomes) complexes play a crucial role in organizing and condensing DNA in eukaryotic cells.
DNA is packaged into linear chromosomes, which must be condensed and segregated properly during the cell cycle.
SMC complexes are evolutionarily ancient and include:
Cohesin
Condensin I
Condensin II
Interphase Function
During interphase, cells are actively growing and expressing genes.
SMC proteins help in looping DNA and bringing together regulatory elements to aid in gene expression and chromatin organization.
Mitosis Function
As cells enter mitosis, condensins start forming DNA loops to condense chromatin into chromosomes.
Condensin I forms large loops, while Condensin II forms smaller loops, resulting in highly compacted mitotic chromosomes.
Cohesin holds the two sister chromatids together until a signal triggers their separation.
Structure & Evolution
SMC complexes share a common evolutionary origin and consist of a heterodimer of long SMC proteins. They have similar molecular architecture.
In cohesin, this includes SMC1 and SMC3, which have ATPase activity.
The kleisin subunit binds to the SMC proteins, forming a ring-like structure.
Ring Model
Cohesin rings encircle both sister chromatids, ensuring they remain together until separation.
Condensin rings loop and compact single DNA molecules to facilitate chromosome condensation.
condensin and chromosomal condensation?
Condensin complexes compact DNA along its length to form mitotic chromosomes.
Their activity is regulated by mitotic kinases.
Condensin I vs. Condensin II
Condensin II is nuclear and begins condensing chromosomes at mitotic entry, before Condensin I.
It forms loops and folds a single chromatid on itself, keeping it organized into large loops.
As these loops form, the chromosome becomes thicker and shorter.
Condensin I is cytoplasmic and cannot access chromosomes until nuclear envelope breakdown (NEBD).
After NEBD, Condensin I enters the nucleus and works alongside Condensin II to form smaller loops, further compacting chromosomes.
cohesin?
The cohesin complex encircles the sister chromatids, holding them together until chromosome segregation during mitosis.
Cohesion Establishment and Protection
Cohesion between the two sister chromatids is established in S phase when the second strand of DNA is synthesized.
The cohesin complex is deposited to circle the chromatids together during DNA replication.
Serpin proteins protect cohesin from being removed by a factor called WAPL during mitosis.
As the cell progresses into mitosis, Serpin gets inactivated, allowing WAPL to remove cohesin almost throughout the entire chromosomes, except at the centromeres.
At the centromeres, SGO1 (Shugoshin 1) protects cohesin to ensure it remains intact during this stage.
Metaphase to Anaphase Transition
By metaphase, X-shaped chromosomes align at the metaphase plate, and microtubules attach to the kinetochores of the chromosomes.
Cohesion in the chromosome arms is removed, but cohesin remains at the centromeres during metaphase.
Separase, a protease, is required to cleave cohesin during anaphase, enabling the sister chromatids to separate and allowing chromosomal segregation.
This is a critical transition for ensuring the correct segregation of chromosomes into daughter cells.
Checkpoint Mechanism
Cells monitor the cohesion status of the chromatids to ensure proper alignment and attachment to the mitotic spindle before proceeding with chromosome separation.
mitotic spindle?
The mitotic spindle is the machinery responsible for chromosome separation during mitosis. It is made of microtubules.
Structure of the Mitotic Spindle
The mitotic spindle is bipolar, meaning it has two poles, each originating from centrosomes.
The minus ends of the microtubules are located at the centrosomes, while the plus ends extend toward the chromosomes.
Types of Microtubules in the Mitotic Spindle
Kinetochore Microtubules:
These microtubules attach to the kinetochores (protein complexes on the chromosomes) and are responsible for moving chromosomes during cell division.
These microtubules help in chromosome segregation by pulling the chromosomes toward opposite spindle poles.
Interpolar Microtubules:
These microtubules interact with microtubules from the opposite spindle pole, providing stability to the spindle structure and helping to maintain its integrity during cell division.
Astral Microtubules:
These microtubules radiate outward from the centrosomes, exploring the rest of the cell.
They play a role in spindle positioning and rotation, helping to orient the spindle correctly within the cell.
They also help in the placement of the spindle in the center of the cell, ensuring equal distribution of chromosomes.
centrosomes?
Centrosomes are the primary microtubule organizing centers (MTOCs) in the cell. They play a crucial role in organizing the mitotic spindle during cell division.
Centrosomes nucleate and anchor spindle microtubules through the γ-tubulin ring complexes.
γ-tubulin (gamma-tubulin) is a protein that forms a ring complex at the centrosome. This complex serves as a nucleation site where microtubules grow from.
The microtubules that emanate from the centrosome are stabilized by γ-tubulin and are important for the formation of the mitotic spindle.
These microtubules grow from the minus end, with the plus end extending outward toward the chromosomes and other components of the cell.
Function of Centrosomes in Mitotic Spindle Organization
The centrosome is essential for organizing the mitotic spindle, ensuring the proper orientation and segregation of chromosomes during mitosis.
