Mitosis Flashcards
What are the 2 phases of anaphase?
- Chromosomes condensation
- Sister-chromatid resolution
What is a chromosome?
linear DNA molecule
What is a centromere?
region where the spindle attaches
What are homologous structures?
have the same genes arranged in the same order (1 inherited from father, 1 from mother)
What are chromatids?
newly copied DNA strands still joined to each other by a centromere
How do cyclins lead to protein activation?
cyclins bind to CDKs (cyclin-dependent kinase), which leads to activation of the protein by phosphorylation
How do you stop activation of a protein which drives the transition between different stages of the cell cycle?
Destruction of the cyclin will stop activation of the protein.
What controls the transition between metaphase & anaphase?
controlled by APC (anaphase-promoting complex)
What complex is involved in driving entry into mitosis
M-Cdk trigger
What occurs following the activation of the M-Cdk trigger?
- assembly of the mitotic spindle
- each sister chromatid is attached to an opposite pole
- chromosome condensation
- breakdown of the nuclear envelope
- rearrangement of the actin cytoskeleton + Golgi
Describe the process by which M-cyclin/Cdk triggers entry into mitosis
- M-cyclin/Cdk1 complex formed
- Cdk-activating kinase (CAK) can then phosphorylate the complex at an activating location.
- Cdc25 then gets phosphorylated, which will then attach to Cdk, removing the phosphate from the M-Cdk complex, activating it.
- On another hand, the phosphorylation of an inhibitory location can take place as a result of the action of Cdk-inhibitory kinase (Wee1). This inhibits its action.
What activates Cdc25?
S-Cdk complexes. Once started positive feedback will inhibit Wee1 & activate more Cdc25
How does APC (anaphase-promoting complex) drive transition form metaphase to anaphase?
Driven by protein destruction - cyclin is targeted, which leads to the cyclin changing in its protein expression (NOT THE Cdk).
How is cyclin destroyed during the APC (anaphase-promoting complex)?
Ubiquitin attaches to the cyclin, leading to destruction (a tag for destruction)
What are 2 targets for APC?
- S&M cyclins (if destroyed, most CDKs are inactivated)
- Securin (protects the protein linkages that hold sister chromatids together, therefore, its destruction activates a protease that separates the sister chromatids)
What is the 2-hit hypothesis?
Most genes need mutations on BOTH alleles to cause a phenotypic change?
What is a loss of a single tumour-suppressor gene?
Loss of heterozygosity
What do we get a loss-of-heterozygosity?
- either a second hit
- loss of one of the chromosomes that still have a wild type allele
What is the phrase given when chromosomes don’t separate properly?
Chromosome non-disjunction
What constitutes a successful mitosis?
sister chromatids going to opposite poles
What technique is used to attach the 1 kinetocore to spindle pole?
Trial & error
How is appropriate spindle fibre attachment sensed?
tension
Describe what correct spindle attachment would consist of?
- kinetocores pulled in opposite directions (BUT sister chromatids resists –> tension)
Describe what incorrect spindle attachment would consist of?
Tension is lower (loosens the microtubule attachment size)
What occurs during Anaphase A?
Separase breaks the cohesin bridges between chromosomes, and the kinetochore microtubules shorten, dragging the chromosomes towards the two poles of the cell.
What occurs during Anaphase B?
Astral microtubules slide across each other, further pulling the cells apart.
What process should normally occur when there is a loss of heterozygosity by non-disjunction?
Elimination by apoptosis
What do loss of heterozygosity by mitotic recombination & gene conversion have in common?
They both lead to 2nd hit - 2nd copy inactivation
