2: Cell cycle Flashcards
Which factors influence the speed of cell devision?
- embryonic vs. adult cell
- complexity of systems (e.g. rapid devision in yeast cells)
- Necessitiy for renewal (intestinal epithelium vs. hepatocytes)
- state of differentiation (e.g. neurons/cardiomyocytes that don’t replicate)
- Tumor cells ?? –> different mechanisms
What happens when the appropriate regulation of cell devision goes wrong?
Which factors might lead to it?
Cancer might develop that
- mutation in TSG/oncogenes (–> + aneupleudy)
- chormosome instability (loss/gain of chromosome)
- abnormal mitosis –> mistake in cell cylce regulatory proteins
- Contact inhibition of growth –> cells don’t stop growing when they reach the edges of a space
What is the cell cycle?
Orderly sequence of events in which a cell duplicates its contents and divides in two
What are the different phases in the cell cycle of an eucariotic cell?
- M Mitosis
- Interphase
- G0
- cell cycle machinery dismantled –> cell fulfils normal function
- G1
- phase (Gap) - Decision point: are specific structures (e.g. centromeres) duplicated?
- S
- DNA dublication
- G2
- phase (Gap) - Decision point
- check new DNA for mistakes
- G0

What happens during the S-phase of the cell cycle?
- DNA replication
- Replication of organelles (e.g. golgi, mitochondria, centromeres)
- Increased protein synthesis
Explain the structure of a centrosome
Consists of two centrioles (barrels of nine triplet microtubules

What is the function of the centrosome?
- microtubule organizing center (MTOC) (also in interphase!!)
- mitotic spindle
Explain the life cycle and replication of the centrosomes
Split in G1 and are fully replicated at the end of S-phase

What happens during the prophase of mitosis?
- condensation of DNA
- centrosomes migrate to opposite sides in cell
- spindels start to form

Explain the formation of the mitotic spindles
- ASTERS form (radial micturtubule arrays) around each centromer –> Microtubule organisation centre)
- Tadial arrays meet
- Polar micrutubules form (= radial microtubules that meet in middle)

What happens during the early prometaphase in the cell cycle?
- Chromosomes aligned at equator of the spindle
In the early:
- break down of nuclear membrane
- spindles are largely complete
- attach of chromosomes to the spindles via kinetochores at the centromer region of chromosome

What happens during the late prometaphase
- Microtubule from opposite pole is captured by sister kinetochore
- Chromosomes attached to each pole congress to the middle
- Chromosome slides rapidly towards center along microtubules
What happes during the anaphase in mitosis?
- Paired chromosomes separate to form two daughter chromosomes
- Cohesin holds sister chromatids together
- There is a anaphase A+ B
What happens during Anaphase A in mitosis?
- Breakdown cohesin (protein that holds togehter sister chromatids)
- Microtubules get shorter
- Daughter chromosomes pulled toward opposite spindle poles

What happens during Anaphase B?
- Daughter chromosomes migrate towards poles
- Spindle poles (centrosomes) migrate apart
- so cytokinesis does not happen too close to chormosomes and they have enough space

What happens during telophase of mitosis?
Chromosomes arrive at spindles
Nuclear envelope resembels
Assembly of contractile ring (for cytokinesis), made of actin and myosin

What happens at the transition out of metaphase before Anaphase can start?
Explain its mechanism
Spindle Assembly checkpoint
- are all chromosomes connected hthe kinetochore?
- When kinetochores are connected they stop signaling
- At the checkpoint it is waited, until there is no more signaling (i.e. all chormonsomes are connected) until Anaphase can start
What are the different factors required in the Spindle Assembly checkpoint?
(aka Mitotic Checkpoint)
- CENP-E (signals when not attached)
- BUB protein kinases (signals when attached)
BUBs dissociate from kinetochore when chromosomes are properly attached to the spindle

Explain the different things that can go wrong at the Spindle assembly checkpoint
Missatachmen of spindles to kinetochore might lead to aneupleudy
- Meroteilic attachment (2 differnt spindels attach to the same chromatid)
- one spindle attaches to both sister chromatids of one chromosomes

How might alterations in the cell cycle lead to aneupleudy?
- errors in DNA or centrosome replication
- might lead to multipolar spindles
- or in aberrant (irrtümliche) citokinesis

Explaint the exploitation of chromosome-missegregation as an anti-cancer treatment
- Inhibition of Checkpoint kinase (CHKE1 and CHKE2)
- Normally : Serine threonine kinase activation holds cells in G2 phase until all is ready
- inhibits attachment-error-correction mechanism
- inhibition leads to untimely cell transition to mitosis –> not ready yet because there is still an error
- Normally : Serine threonine kinase activation holds cells in G2 phase until all is ready
- Taxanes and vinca alkaloids
- Alters microtubule dynamics
- Produces unattached kinetochores
- Causes long-term mitotic arrest.

What if something goes wrong during the cell cycle? e.g Cell is not big enough or DNA damage
- Cell cylce arrest at checkpoints (G1+ spindle checkpoint)
- can be temporarily and resolved e.g. with DNA repair
- Apoptosis
- if DNA damage to great, chromosomal abnormalities or toxic agents
What are the different check points in the cell that drive/ control cell proliferation?
How is that important in cancer?
- G1: Checkpoint in G1 (Growth Factor dependant)
- initiate progession
- G2: Damage of DNA
- M: Sister chromatid alignment
All these checkpoints can be altered by tumors!!

Explain the concept of De-regulation of cell cycle during tumorigenesis
Tumors can inhibit entering into G0 phase where the cell just does its nomal function and promote proliveration








