Notes: Regulation Of The Cell Cycle

CH 12 NOTES, part 2:Regulation of the Cell Cycle (12.3)

12.3 - The eukaryotic cell cycle isregulated by a molecular controlsystem The frequency of cell division varies with thetype of cell: human skin cell: every 24-28 hrs human nerve cell: never after maturity frog embryo cell: every hour These cell cycle differences result fromregulation at the molecular level

Evidence for CytoplasmicSignals The cell cycle appears to be driven byspecific chemical signals present in thecytoplasm Some evidence for this hypothesiscomes from experiments in whichcultured mammalian cells at differentphases of the cell cycle were fused toform a single cell with two nuclei

Experiment 1Experiment 2SG1MG1SSMMWhen a cell in the S phase wasfused with a cell in G1, the G1cell immediately entered theS phase—DNA was synthesized.When a cell in the M phasewas fused with a cell in G1,the G1 cell immediately beganmitosis—a spindle formed andchromatin condensed, eventhough the chromosome hadnot been duplicated.

The Cell Cycle Control System The sequential events of the cell cycle aredirected by a distinct cell cycle controlsystem, which is similar to a built-in clock The clock has specific checkpoints wherethe cell cycle stops until a go-ahead signalis received

G1 checkpointControlsystemG1MM checkpointG2 checkpointG2S

For many cells, the G1 checkpoint seemsto be the most important one If a cell receives a go-ahead signal at the G1checkpoint, it will usually complete the S,G2, and M phases and divide If the cell does not receive the go-aheadsignal, it will exit the cycle, switching into anondividing state called the G0 phase

G0G1 checkpointG1If a cell receives a go-aheadsignal at the G1 checkpoint,the cell continues on in thecell cycle.G1If a cell does not receive ago-ahead signal at the G1checkpoint, the cell exits thecell cycle and goes into G0, anondividing state.

Researchers have identified severalfactors that can influence cell division:1) Chemical factors2) Physical Factors

External CHEMICAL FACTORS– Nutrients & Growth Factors: if essential NUTRIENTS are left out of theculture medium, cells will not divide. GROWTH FACTORS specific regulatoryproteins released by certain body cells thatstimulate other cells to divide PDGF (platelet derived growth factor)binds to cell membrane receptors andstimulates cell division in fibroblasts (i.e. as aresponse to heal wounds)

Internal CHEMICAL FACTORS- Cyclins & Cdks Two types of regulatory proteins areinvolved in cell cycle control: CYCLINS andCYCLIN-DEPENDENT KINASES (Cdks) The activity of cyclins and Cdks fluctuatesduring the cell cycle

MG1SG2MG1SG2MMPF activityCyclinTimeFluctuation of MPF activity and cyclin concentrationduring the cell cycle

CdkDegradedcyclinG2CdkcheckpointCyclin isdegradedMPFCyclinMolecular mechanisms that help regulate the cell cycle

Stop and Go Signs: Internal andExternal Signals at the Checkpoints EX. of internal signal: kinetochores notattached to spindle microtubules send amolecular signal that delays anaphase(by keeping an anaphase-promotingcomplex (APC) in an inactive state) EX. of external signal: PDGF released bydamaged/injured body cells stimulatesfibroblast growth to heal injury

PHYSICAL FACTORS: crowding inhibits cell division in what iscalled DENSITY-DEPENDENTINHIBITION.Normal sheet (upper,left) and "cell crowding"in three grades ofexpression

many animal cells exhibit ANCHORAGEDEPENDENCE (cells must adhere to asubstratum, such as the surface of aculture dish or the extracellular matrix of atissue)**Cancer cells areabnormal and do notexhibit densitydependent inhibitionor anchoragedependent inhibition.

Cells anchor to dish surface anddivide (anchorage dependence).When cells have formed a completesingle layer, they stop dividing(density-dependent inhibition).If some cells are scraped away, theremaining cells divide to fill the gap andthen stop (density-dependent inhibition).Normal mammalian cells25 µm

Cancer cells do not exhibitanchorage dependenceor density-dependent inhibition.25 µmCancer cells

CANCER: cancer cells do notrespond to body’scontrol mechanisms cancer cells divideexcessively, invadeother tissues, and cankill the organism if leftunchecked

HOW do they do this? some cancer cells may make their owngrowth factors; cancer cells may have an abnormalgrowth factor signaling system; cancer cells divide indefinitely (asopposed to normal cells, which typicallydivide about 20-50 times before theystop).

Normally, the immune system recognizes anddestroys transformed or mutated cells which aregrowing abnormally if abnormal cells evade the immune system, theymay form a TUMOR.Bronchustumor

if the cells remain at theoriginal site, the mass iscalled a BENIGNTUMOR and can becompletely removed bysurgery. if the tumor cells haveinvaded other tissues /organs, it is aMALIGNANT TUMOR.

Properties of malignant tumors: excessive cell proliferation may have unusual numbers ofchromosomes may have abnormal metabolism abnormal cell surface changes(i.e. lost attachments to neighboringcells) they cease to function in anyconstructive way

if cancer cells separatefrom the original tumorand spread into othertissues, entering theblood and lymphvessels, they mayinvade other parts ofthe body and developinto new tumors thisis called METASTASIS.

Cancer is the 2nd leading cause ofdeath in the U.S. It can affect any tissue,but the most commonlyaffected are: lung colon breast prostate

Treatments surgery (for benign tumors) radiation chemotherapy

**Although we do not fully understand how anormal cell is transformed into a cancerouscell, it seems clear that there is analteration of genes that somehow influencethe cell-cycle control system.

**Factors which can cause an “alteration ofgenes” (a.k.a. MUTAGENS) include:1) Chemicals2) Radiation

Examples of Chemical Mutagens:– cigarette smoke– DDT– chewing tobacco– pollution– chromium-6

Examples of Radiation Mutagens:– sun (UV rays)– nuclear waste– x-raysskin cancer caused bytoo much sunspots: sun damage

HHMI Website:Biointeractive.org CELL CYCLE “Click & Learn”

12.3 - The eukaryotic cell cycle is regulated by a molecular control system The frequency of cell division varies with the type of cell: human skin cell: every 24-28 hrs human nerve cell: never after maturity frog embryo cell: every hour