lecture 8 - the cell cycle and apoptosis Flashcards
What is cell cycling?
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 high stress loads).
-cell numbers need to increase when we have a wound
What is the sequence of phases of the cell cycle?
Sequence of phases:
G1, (G0), S, G2, M
G1: Gap 1 - 11 hours G0: Resting S: DNA synthesis - 8 hours G2: Gap 2 - 4 hours M: Mitosis - 1 hour
What is interphase?
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.
Describe G1
Gap phase 1 (G1)
2n DNA
G1 can be extremely short (e.g. in rapidly dividing embryonic cells) or last weeks, even years.
Cell activities during G1:
Cell growth and synthesis of macromolecules
Detection of DNA damage and repair
G1 (Restriction) Checkpoint: DNA damage (if cannot be repaired, cell self-destructs (apoptosis)) Suitable environmental conditions If checkpoints passed, cell becomes committed to DNA synthesis
Describe G0
Gap phase 0 (G0)
A Time-Out 2n DNA Cells can leave the cell cycle at G1. Become non-dividing cells in quiescent state. Still living, functional cells. Can last for weeks, years.
G0 cells can re-enter the cell cycle with correct signals, such as a growth factor.
Cancer cells do not enter G0.
Describe S
Synthesis phase (S) DNA replication to give 4n complement Start of S Phase, each chromosome = One coiled DNA double helix (chromatid) End of S Phase, each chromosome = Two identical coiled DNA double helices (sister chromatids)
Describe G2
Gap phase 2 (G2)
4n complement of DNA
Preparation for mitosis
Checkpoint for unreplicated and damaged DNA - prevents cells entering mitosis with faulty DNA - helps maintain genomic stability.
Describe mitosis
Mitosis phase (M) Mitosis: Prophase Metaphase Anaphase Telophase Cytokinesis (cytoplasm divides to give two daughter cells)
Spindle assembly checkpoint
Checkpoint for mis-aligned chromosomes
Over half of mitosis is spent in prophase, then metaphase and anaphase are very brief, followed by a relatively long telophase. Mitosis maintains a constant amount of genetic material and a constant set of genes from cell generation to cell generation. Mitosis is a highly ordered process in which one copy of each duplicated chromosome segregates into both daughter cells. Following chromosome replication, there are two genetically identical diploid cells.
What are mitogens?
Mitogens stimulate cell division
Many cell signalling molecules can have mitogenic properties; they induce cell proliferation by promoting entry into the Cell Cycle.
Platelet-Derived Growth Factor (PDGF), widespread effects (e.g.) during wound healing.
FGF (see HVI lectures) – pleiotropic effects.
Members of the TGF-β family can stimulate cell proliferation or inhibit proliferation, depending on cell type, concentration.
Erythropoietin: more selective - induces proliferation of BFU-E and CFU-E (See Lecture 10).
How is the cell cycle regulated?
Cell cycle progression is regulated by cyclins and
cyclin dependent kinases (Cdks).
Different cyclins associate with different Cdks during the phases of the cell cycle.
RB = Retinoblastoma protein, a tumour suppressor, keeps cell cycle in check RB dephosphorylated (active) Prevents G1-S transition RB phosphorylated (inactive)
What is the cellular equilibrium?
proliferation -> differentiation -> death
What is the difference between apoptosis and necrosis?
Apoptosis: Physiological Cellular condensation Nuclear fragmentation Rapid phagocytosis Lack of inflammation
Necrosis: Pathological Organelles swell Membranes rupture Leakage of cell contents Marked inflammation
What are the different Morphological Features of Cell Death between apoptosis and necrosis?
Necrotic: Disruption of plasma membrane Intact nucleus Lesions Even nuclear pores
Apoptotic:
Change in nuclear structure
Blebbing of cell surface membrane
Clustered nuclear pores
What is necrosis?
Pathologically induced, occurs in response to tissue damage.
Often involves groups of cells that swell and burst, releasing their intracellular contents and frequently induces inflammation.
e.g. Cerebral infarction (stroke)
What are the roles of apoptosis?
Development
Tissue homeostasis
Removal of damaged cells
Elimination of premalignant cells
