regulation of cell division - matsuk12.us · ap biology g. 2. s. g. 1. m. metaphase. prophase....
Post on 18-Jul-2021
1 Views
Preview:
TRANSCRIPT
2006-2007AP Biology
Regulation of Cell Division
AP Biology
Coordination of cell divisionA multicellular organism needs to coordinate cell division across different tissues & organs
critical for normal growth,development & maintenance
coordinate timing ofcell divisioncoordinate rates ofcell divisionnot all cells can have the same cell cycle
AP Biology
G2
S G1
Mmetaphase
prophaseanaphase
telophase
interphase (G1 , S, G2 phases)mitosis (M)cytokinesis (C)
C
Frequency of cell division varies by cell typeembryo
cell cycle < 20 minuteskin cells
divide frequently throughout life12-24 hours cycle
liver cellsretain ability to divide, but keep it in reservedivide once every year or two
mature nerve cells & muscle cellsdo not divide at all after maturitypermanently in G0
Frequency of cell division
AP Biology
Overview of Cell Cycle ControlTwo irreversible points in cell cycle
replication of genetic materialseparation of sister chromatids
Checkpointsprocess is assessed & possibly halted
centromere
sister chromatids
single-strandedchromosomes double-stranded
chromosomes
There’s no
turning back,
now!
AP Biology
Checkpoint control systemCheckpoints
cell cycle controlled by STOP & GOchemical signals at critical pointssignals indicate if key cellular processes have been completed correctly
AP Biology
Checkpoint control system3 major checkpoints:
G1/Scan DNA synthesis begin?
G2/Mhas DNA synthesis been completed correctly?commitment to mitosis
spindle checkpointare all chromosomes attached to spindle?can sister chromatids separate correctly?
AP Biology
G1 /S checkpointG1/S checkpoint is most critical
primary decision point“restriction point”
if cell receives “GO” signal, it dividesinternal signals: cell growth (size), cell nutritionexternal signals: “growth factors”
if cell does not receivesignal, it exits cycle & switches to G0 phase
non-dividing, working state
AP Biology
G0 phase
MMitosis
G1Gap 1
G0Resting
G2Gap 2
SSynthesis
G0 phasenon-dividing, differentiated statemost human cells in G0 phase
liver cellsin G0, but can be “called back” to cell cycle by external cues
nerve & muscle cellshighly specializedarrested in G0 & can never divide
AP Biology
How do cells know when to divide?cell communication signals
chemical signals in cytoplasm give cuesignals usually mean proteins
activatorsinhibitors
Activation of cell division
experimental evidence: Can you explain this?
AP Biology
“Go-ahead” signalsProtein signals that promote cell growth & division
internal signals“promoting factors”
external signals“growth factors”
Primary mechanism of controlphosphorylation
kinase enzymeseither activates or inactivates cell signals
AP Biology
Cell cycle signals Cell cycle controls
cyclinsregulatory proteinslevels cycle in the cell
Cdk’scyclin-dependent kinasesphosphorylates cellular proteins
activates or inactivates proteinsCdk-cyclin complex
triggers passage through different stages of cell cycle
activated Cdk
inactivated Cdk
AP Biology
Cyclins & CdksInteraction of Cdk’s & different cyclins triggers the stages of the cell cycle
Leland H. Hartwellcheckpoints
Tim HuntCdks
Sir Paul Nursecyclins
1970s-’80s | 2001
AP Biology
Cdk / G1cyclin
Cdk / G2cyclin (MPF)
G2
S
G1
CM
G2 / M checkpoint
G1 / S checkpoint
APC
Active Inactive
ActiveInactive
InactiveActive
mitosis
cytokinesis
MPF = Mitosis Promoting FactorAPC = Anaphase Promoting Complex
• Replication completed• DNA integrity
Chromosomes attached at metaphase plate
Spindle checkpoint
• Growth factors• Nutritional state of cell• Size of cell
AP Biology
Cyclin & Cyclin-dependent kinasesCDKs & cyclin drive cell fromone phase to next in cell cycle
proper regulation of cell cycle is so key to life that the genes for these regulatory proteinshave been highly conserved throughevolutionthe genes are basically the same in yeast, insects, plants & animals (including humans)
AP Biology
External signalsGrowth factors
coordination between cellsprotein signals released by body cells that stimulate other cells to divide
density-dependent inhibitioncrowded cells stop dividingeach cell binds a bit of growth factor
not enough activator left to trigger division in any one cell
anchorage dependenceto divide cells must be attached to a substrate
“touch sensor” receptors
AP Biology
E2F
nucleuscytoplasm
cell division
nuclear membrane
growth factor
protein kinasecascade
nuclear pore
chromosome
Cdkcell surfacereceptor
P
PP
P
P
E2FRb
Rb
Growth factor signals
AP Biology
Example of a Growth FactorPlatelet Derived Growth Factor (PDGF)
made by platelets in blood clotsbinding of PDGF to cell receptors stimulates cell division in fibroblast (connective tissue)
heal wounds
Don’t forgetto mention
erythropoietin
!(EPO)
AP Biology
Growth Factors and CancerGrowth factors can create cancers
proto-oncogenesnormal growth factor genes that become oncogenes (cancer-causing) when mutatedstimulates cell growthif switched “ON” can cause cancerexample: RAS (activates cyclins)
tumor-suppressor genesinhibits cell divisionif switched “OFF” can cause cancerexample: p53
AP Biology
Cancer & Cell GrowthCancer is essentially a failureof cell division control
unrestrained, uncontrolled cell growthWhat control is lost?
lose checkpoint stopsgene p53 plays a key role in G1/S restriction point
p53 protein halts cell division if it detects damaged DNAoptions:
stimulates repair enzymes to fix DNAforces cell into G0 resting stagekeeps cell in G1 arrestcauses apoptosis of damaged cell
ALL cancers have to shut down p53 activity
p53 discovered at Stony Brook by Dr. Arnold Levine
p53 is the
Cell Cycle
Enforcer
AP Biology
DNA damage is causedby heat, radiation, or chemicals.
p53 allows cellswith repairedDNA to divide.
Step 1
DNA damage iscaused by heat,radiation, or chemicals.
Step 1 Step 2
Damaged cells continue to divide.If other damage accumulates, thecell can turn cancerous.
Step 3p53 triggers the destruction of cells damaged beyond repair.
ABNORMAL p53
NORMAL p53
abnormalp53 protein
cancercell
Step 3The p53 protein fails to stopcell division and repair DNA.Cell divides without repair todamaged DNA.
Cell division stops, and p53 triggers enzymes to repair damaged region.
Step 2
DNA repair enzymep53protein p53
protein
p53 — master regulator gene
AP Biology
Development of CancerCancer develops only after a cell experiences ~6 key mutations (“hits”)
unlimited growthturn on growth promoter genes
ignore checkpointsturn off tumor suppressor genes (p53)
escape apoptosisturn off suicide genes
immortality = unlimited divisionsturn on chromosome maintenance genes
promotes blood vessel growthturn on blood vessel growth genes
overcome anchor & density dependenceturn off touch-sensor gene
It’s like an
out of control
car!
AP Biology
What causes these “hits”? Mutations in cells can be triggered by
UV radiationchemical exposureradiation exposureheat
cigarette smokepollutionagegenetics
AP Biology
TumorsMass of abnormal cells
Benign tumor abnormal cells remain at original site as a lump
p53 has halted cell divisionsmost do not cause serious problems &can be removed by surgery
Malignant tumorscells leave original site
lose attachment to nearby cellscarried by blood & lymph system to other tissuesstart more tumors = metastasis
impair functions of organs throughout body
AP Biology
Traditional treatments for cancersTreatments target rapidly dividing cells
high-energy radiationkills rapidly dividing cells
chemotherapystop DNA replicationstop mitosis & cytokinesisstop blood vessel growth
AP Biology
New “miracle drugs”Drugs targeting proteins (enzymes) found only in cancer cells
Gleevectreatment for adult leukemia (CML)& stomach cancer (GIST)1st successful drug targeting only cancer cells
Novartes
without Gleevec
with Gleevec
2006-2007AP Biology
Any Questions??
top related