checkpoint - specific points where cell cycle can be put on hold
- 2 irreversible points - replication of genetic material, sister chromatid separation
- kinase - adds phosphate
- phosphatase - takes away phosphate
- phosphorylation/dephosphorylation >> activate/deactivate proteins >> drives cell cycle
- cyclin - proteins displaying characteristic patterns of synthesis/degradation like the cell cycle
- cyclin-dependent kinase (Cdk) - enzyme that controls passage through the checkpoints
- multicellular organisms respond to more external signals and use more Cdk’s than unicellular organisms
G1/S checkpoint - main point where the cell decides whether or not to divide
- links cell division to cell growth
- aka “restriction point” (R point) in animals
- aka “start” in yeasts
- decision to replicate genome >> decision to replicate
- internal signals - nutritional cell state, cell size
- external signals - factors that promote cell growth/division
G2/M checkpoint - point where cell commits to mitosis
- can halt if DNA not replicated correctly
- M-phase-promoting factor (MPF) - Cdk that works at this checkpoint; sensitive to substances that disrupt DNA
- removal of inhibitor phosphates acts as signal (damaged DNA >> inhibitory phosphorylation of MPF)
spindle checkpoint – makes sure that all chromosomes attached to spindle for anaphase
- checks to see if all chromosomes are aligned on metaphase plate
- anaphase-promoting complex – transmits signal that removes inhibitors of protease (which destroys the cohesion that holds chromatids together)
growth factors – regulatory signals that stimulate cell division
- triggers intracellular signaling systems
- platelet-derived growth factor (PDGF) – promotes fibroblast growth
- overrides cellular controls that normally stop cell division
- most cells need combination of different growth factors to totally promote cell division
cancer – uncontrolled cell growth
- occurs when cell can’t control division
- p53 – gene controlling G1 checkpoint
- tells cell to kill itself (apoptosis) if DNA damage can’t be repared
- prevents development of mutated cells
- mutation in gene allows cancer cells to continue dividing
- oncogenes – genes that can cause cells to be cancerous
- proto-oncogenes – normal cellular genes; becomes oncogenes when mutated
- can cause growth receptors to continually stay on, even w/o growth factor
- can mutate proteins involved in signal cascades between receptor and Cdk
- tumor-suppressor genes – normally inhibits the cell cycle, recessive to proto-oncogenes
- retinoblastoma susceptibility gene (Rb) – only needs a single mutated copy to lead to cancer
- single cancerous cell in retina >> retinoblastoma forms
- Rb protein – aka “pocket protein,” has binding pockets for other proteins
Subject:
Subject X2:
