Cell And Developmental Biology, Lecture 8

Front 1

1) 3 stages in cellular equilibrium?

2) How does cancer differ?

3) Purpose of cell cycling?

Back 1

1) Proliferation, differentiation, death.

2) Cancer is a disruption of cellular equilibrium, caused by deregulated cell cycle control.

3) New cells produced by cell division:To replace lost cells or damaged tissue(e.g. red blood cells live about 3 months, muscle tissue damaged through highstress loads).

Front 2

1) The sequence of phases in the cell cycle? And approximate times of each.

2) Non mitotic cells are in?

Back 2

1) G1: Gap1 (11 hours)

G0: Resting (varied)

S: DNAsynthesis (8 hours)

G2: Gap2, cell growth(4 hours)

M: Mitosis (1 hour)

24 hours total= population doubling time.

2) Non-mitotic cells are in Interphase. Interphase includes G0, G1, S and G2.

During interphase, the cell grows,carries out its normal functions, DNA replicated.

Front 3

1) The cell cycle checkpoints?

Back 3

1) M= checks for chromosome misalignment- to see if the spindle fibers are fully engaged with the centromeres.

G1= Check for damaged DNA

G2= Check for unreplicated or damaged DNA.

Front 4

1) G1 in more detail, cellular activities and expand on checkpoint.

Back 4

1) Gapphase 1 (G1)

2n DNA. G1 can be extremely short (e.g. inrapidly dividing embryonic cells) or last weeks, even years.

Cell activities during G1:

Cellgrowth and synthesis of macromolecules. Detectionof DNA damage and repair

G1 (Restriction) Checkpoint:

•DNAdamage (if cannot be repaired, cell self-destructs (apoptosis))•Suitableenvironmental conditions

Ifcheckpoints passed, cell becomes committed to DNA synthesis

Front 5

1) G0 phase in more detail?

Back 5

1) ATime-Out

2n DNA. Cells can leave the cell cycle at G1.Become non-dividing cells in quiescentstate.Still living, functional cells.Can last for weeks, years.G0 cells can re-enter the cell cycle withcorrect signals, such as a growth factor.Cancer cells do not enter G0.

Front 6

1) S phase in more detail? Chromosome structures at beginning and end of phase?

Back 6

1) Synthesisphase (S)

DNA replication to give 4n complement.

Startof S Phase, each chromosome = One coiled DNA double helix (chromatid).

Endof S Phase, each chromosome = Two identical coiled DNA double helices (sister chromatids)

Front 7

1) G2 phase in more detail and checkpoint?

Back 7

1) Gapphase 2 (G2)

4n complement of DNA

Preparation for mitosis

Checkpointfor unreplicatedand damaged DNA -prevents cells entering mitosis with faulty DNA - helps maintain genomic stability.

Front 8

1) Brief overview of each stage of mitosis (no extra detail of the mini-prophase-stages).

Back 8

1) Prophase- chromosomes condense (36 minutes).

Metaphase- chromosomes attach to spindle fibers and align on the equator. (3 minutes)

Anaphase- Sister chromatids pulled to opposite poles by spindle fibers. (3 minutes)

Telophase- Nuclear membrane reforms, and subsequently a cell plate is laid down between daughter cells (cytokinesis)- 18 minutes.

G1(interphase) nuclear envelope intact, chromosomes not condensed andindistinguishable.Mchromosomes condensed.

Front 9

1) Mitogens? Examples?

Back 9

1) Mitogens stimulate cell division.

Manycell signallingmolecules can have mitogenic properties; they induce cellproliferation by promoting entry into the CellCycle.

Platelet-Derived Growth Factor (PDGF),widespread effects (e.g.) during wound healing.

FGF(see HVI lectures) – pleiotropic effects.

Membersof the TGF-β family can stimulate cell proliferationor inhibit proliferation, depending on cell type, concentration.

Erythropoietin:more selective - induces proliferation of BFU-E and CFU-E (See Lecture 10).

Front 10

1) Cell cycle control, Tim Hunt and sea urchin experiments.

Back 10

1) Cell cycle progression is regulated by cyclinsand cyclindependent kinases (Cdks).

Different cyclins associate withdifferent Cdksduring the phases of the cell cycle.

Protein samples taken at different times after fertilisation, and proteins were separated by time. You could see fluctuating protein expression levels of cyclin.

Front 11

1) Retinoblastoma protein during the cell cycle?

Back 11

1) At the end of mitosis RB is dephosphorylated (active), and prevents G1-S transition. In G1 mitotic activators stimulate the synthesis of cyclin D, a p21 tumour suppressor can inactivate cyclin D here. Cyclin D and Cdk4 (complex), Cyclin E and Cdk2 (complex) phosphorylate RB, inactivating it.

Once R (the restriction point) is passed, the cell cycle proceeds and Cdk2/cyclin A stimulates DNA replication.

Cdk1 and cyclin B initiates mitosis.

Front 12

1) Apoptosis, and necrosis?

Back 12

1) Apoptosis

Physiological

Cellularcondensation

Nuclearfragmentation

Rapidphagocytosis

Lackof inflammation

Necrosis

Pathological Organelles swell

Membranes rupture

Leakage of cell contents

Marked inflammation

Front 13

1) Morphological features of cell death?

Back 13

1) Necrotic? Disruption of plasma membrane, intact nucleus, lesions, evenly spaced nuclear pores.

Apoptotic? undergo a well-defined series of morphological changes. Chromatin compaction and segregation, condensation of cytoplasm, nuclear fragmentation, blebbing, clustered nuclear pores.

Front 14

1) What is necrosis in reponse to?

2) Roles of Apoptosis?

Back 14

1) Pathologically induced, occurs inresponse to tissue damage.Often involves groups of cells that swelland burst, releasing their intracellular contents and frequently inducesinflammation.

2) Development (e.g- formation of finger digits), tissue homeostasis, removal of damaged cells, elimination of premalignant cells.