Mechanisms of Disease Flashcards
Explain the cell cycle, its checkpoints and its regulation by both mitogenic and growth inhibitory factors
interphase => PMAT (prophase, metaphase anaphase telophase, cytokinesis) (increase in DNA quantity)
mitosis => division of cells (increase in number of cells)
CHECKPOINTS:
S phase = synthesis phase to ensure correct replication of DNA (forming 4n)
G1 / G2 = verification
G0 = dormant state until cell duplication is needed (can re-enter cell cycle)
cyclin cdk complex causes phosphorylation of specific substrate (RB RETINOBLASTOMA) = release of E2F = exprsn of S-phase proteins which signals for DNA replication to commence which allows checkpoints to continue
- restriction point = verifies potential DNA DAMAGE
Define drugs acting on the cell cycle
PACITAXEL = acts on polymerase microtubule formation
CISPLATIN = attachement on to DNA lengthwise which prevents repair mechanisms and unzips section of DNA = proliferation stops
Explain key molecular events in the regulation of the cell cycle and apoptosis
APOPTOSIS
1. cell shrinkage = breakdown of cytoskeleton
2. organelles packaged w/in membrane bound vesicles = no leakage of components = signals phagocytosis
3. cell fragmentation
caspase X = activation of caspase Y = downstream signalling to cleaving lamina proteins, myoglobin, intracellular enzymes (lactate dehydrogenase, creatinine kinase) and membrane breakdown
BCL = family comprised of pro and anti-apoptosis signalling
(BAD, BCL-2) (BAX)
Explain mechanisms by which growth control can be disrupted in neoplasia
neoplasia = development of benign tumours
more cells / larger cells
reduced apoptosis
reduced cell cycle arrest
reduced expression and phosphorylation of p53 = reduced mismatch repair or DNA damage verification
Define the response to DNA damage
dna damage?
expression of cdk CHECK2 pauses cell cycle
YES / NO
NO = continue
if YES = How has damage occurred? > initiate mismatch repair = phosphorylation of p53 in response to mutagen damage = cell cycle arrest
