Mitosis Flashcards
What is a chromosome?
linear DNA molecule
Centromere
region where spindle attaches
Homologous chromosomes
‘same’ genes arranged in same order, 1 from father 1 from mother
Chromatids
newly copied DNA strands still joined by a centromere
Describe prophase
condensation of sister chromatids (identical copies)
Describe metaphase
attachment of the mitotic spindle to the kinetochore by microtubules
Describe anaphase
separation of sister chromatids to opposite poles
Describe telophase
nuclear envelope reassembly, start of cytokinesis
What does M-Cdk (or MPF) trigger?
Entry into mitosis:
Assembly of mitotic spindle (allow chromosomes to align + separate)
Each sister chromatid is attached to opposite pole
Chromosome condensation
Breakdown of the nuclear envelope
Rearrangement of the actin cytoskeleton + golgi
Describe how M-cdk triggers into mitosis
- M-cdk levels increase through G2 and M phase (due to increase in cyclin B expression, the cylcin that binds with M-Cdk)
- Cak adds an activating phosphate to M-Cdk
- Wee1 adds an inhibitory phosphate
- M-cdk is inactive
- Cdc25 removes the inhibitory phosphate from M-Cdk, activating it
- This creates a positive feedback loop where Cdc25 is activated more and wee1 is inhibited
What is the metaphase/anaphase transition driven by?
protein destruction
Why is securin destroyed in the metaphase/anaphase transition?
Its destruction activates a protease that separates the sister chromatids = can now be pulled apart
Describe the 2-hit hypothesis.
most genes need mutations on BOTH alleles to cause phenotypic change
Describe a loss of heterozygosity (LOH)
change in chromosomes that is working towards homozygosity (2 mutant alleles)
What is hemizygosity?
the loss of the allele = 1 mutant copy
What is chromosome non-disjunction?
Chromosome ends up in wrong daughter cell e.g lagging chromosomes during anaphase
Describe LOH by mitotic recombination
(G2, M phases)
→ associated with meiosis but happens here also
(pic)
What are the 3 main structural components of the mitotic spindle?
Interpolar microtubules
Astral microtubules
Kinetochore microtubules
Describe the function of interpolar microtubules in mitotic spindles
slide past each other to separate the chromatids
Describe the function of astral microtubules in mitotic spindles
Contact cell cortex to position the spindle (anchor)
Describe the function of kinetochore microtubules in mitotic spindles
attach to the chromosome at kinetochore (centromeres)
describe how inappropriate attachment of the spindles are sensed
→ Tension
Correct attachment:
Kinetochores pulled in opposite directions
But, sister chromatids resist = tension
Incorrect attachment:
Tension is lower → inhibitory signal → loosens the microtubule attachment site
Why is the destruction of securin neccessary to the cell cycle?
Securin inhibits separase (which cleaves the cohesin rings holding chromosomes together)
Securin must be depleted before anaphase to ensure chromosome segregation occurs with anaphase
Describe what happens to the kinetochore microtubules in Anaphase A
Kinetochore microtubules shorten & start to pull chromatids apart
Describe what happens to the astral tubules in Anaphase B
astral tubules slide over each other and finally separate the chromatids
What is APC?
Anaphase-promoting complex used in the M/A transition
What does APC destroy and why?
- M cyclins = pushes cell out of anaphase
- Securin = activates separase: separates the sister chromatids allowing them to move to opposite poles
Describe why Cdks are needed in the cell cycle
Cdks are enyzymes, alone = inactive.
Once bound to a cyclin = active and can phosphorylate target proteins making them more/less active
What are the key events of M phase and what are they driven by?
- Spindle forms
- Chromosomes condense
- Nuclear membrane breaks down
= MPF complex drives this
How does APC/C do its job?
It tags proteins with a polyubiquitin chain, marking it for degradation in the proteasome
