BIOL 1441 1st Edition Lecture 21 Outline of Last Lecture I. Cell cycleII. CancerIII. Two main phases of the cell cycleIV. Cellular divisionV. ChromosomesVI. Cell cycleVII. MitosisVIII. Cell cycle regulation/control systemOutline of Current Lecture I. Cyclins and Cyclin-dependent kinasesII. Cell growth-cancer genesIII. MeiosisIV. Gamete productionV. nondisjunctionCurrent LectureI. Cyclins & Cyclin-Dependent Kinasesa. Regulatory proteins involved in cell cycle control:i. Cyclins – concentration varies (cyclically)ii. Cyclin-dependent kinases (Cdks)- concentration constantb. Concentration of cyclins & activity of Cdks fluctuates during the cell cyclei. Cdks always present in the cell at the same concentration, inactiveThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.ii. Need to be attached to a cyclin to be activeiii. Cyclins- concentration fluctuatesiv. Cdks- enzymatic activity fluctuatesc. Cyclins- concentration fluctuates cyclicallyd. Cdks- activity depends on whether or not they are attached to cyclin e. Cdk activity rises and falls with changes in concentration of cyclinsII. Cell Growth- Cancer Genesa. Oncogenes: Mutated or amplified genes involved in cell growth and differentiationi. Makes cells grow/divide constantly- its turned “on” when its not supposed to beii. Proto-oncogene- normal non-mutated oncogeneiii. Dominant - Gain of functionb. Tumor Suppressorsi. Function to inhibit cell growth- cell cycle check points, DNA damage repairii. Recessive - Loss of functioniii. Tumor Suppressor ® Loss of Function1. Two hit hypothesis- must lose function of both allelesa. Mutation (deletion)b. Loss of Heterozygosity (LOH)i. Missegregationii. Mitotic Recombination 2. Cell cycle check points3. Check & repair DNA sequences4. Induce apoptosisiv. Mutation-p531. Transcription factor-detects errors in DNA, decides repair DNA damage or apoptosis (live or die)2. Over 50% all cancers have p53 mutationv. Internal & External Signals at the Checkpoints1. Internal signal- kinetochores not attached to spindle microtubules,send a molecular signal that delays anaphase2. External signals- growth factors, proteins released by certain cells that stimulate other cells to dividea. Density-dependent inhibition- crowded cells stop dividingb. Anchorage dependence- cells must be attached to a substratum in order to dividec. Cancer Cellsi. Exhibit neither density-dependent inhibition nor anchorage dependence1. Grow on top of eachother and don’t stop/don’t flatten outii. Loss of Cell Cycle Controls in Cancer Cells1. Do not respond to the body’s control mechanisms2. Form tumors, masses of abnormal cells within otherwise normal tissueiii. If abnormal cells remain at the original site- benign tumor1. Not secreting hormones/not movingiv. Malignant tumors- invade surrounding tissues & metastasize1. Moves to other parts of the body2. May form secondary tumors3. Gets in blood stream/lymphatic systemd. Cancer Stagesi. Stage 1- small, localizedii. Stage 2- larger, starts invading iii. Stage 3- Invading tissue, angiogenesis(grow in nutrientsiv. Stage 4- metastasis- moved into other organsIII. Meiosisa. Cellular division of gametes i. Egg & spermii. Each have 23 chromosomesb. Fertilization- joining of egg and spermi. Form 1 cell with 46 chromosomesii. Cell divides (mitosis) & develops into fetus (somatic cells)iii. Puberty- meiosis occurs and gametes formc. Two divisionsi. Meiosis Iii. Meiosis IId. Gamete Productioni. Produced in gonads: testes or ovariesii. Males- spermatogenesis, 64 days1. Doesn’t occur until pubertyiii. Spermatogenesis affected by:1. Dietary deficiencies- vitamins B, E and A2. Anabolic steroids3. Cadmium and lead, dioxin, X-rays4. Alcohol & infectious diseasese. Gamete Productioni. Females- oogenesisii. Born with as many oocytes as you will ever haveiii. 20 wks- 7 million eggsf. Gametogenesis- differencesi. Gamete number:1. Spermatogenesis- 4 gametes2. Oogenesis- 1 gamete (3 polar bodies)ii. Start of gamete development:1. Spermatogenesis- occurs throughout adolescence & adulthood2. Oogenesis- begins before birthiii. Timing:1. Spermatogenesis- occurs continuously2. Oogenesis- long interruptions (cycles)IV. Nondisjunctiona. Normal separation of chromosomes in meiosis- disjunctionb. Separation is not normal- nondisjunctionc. Results in the production of gametes- too many of too few of a particular chromosomei. Common mechanism for trisomy or monosomyd. Down Syndrome - trisomy of chromosome 21 e. Klinefelter’s Syndrome - extra X chromosomes in males - XXY, XXXY, XXXXY (1 in every 500 males, only 1 in 1,000 have syndrome)f. Turner’s Syndrome - lacking of one X chromosome in females - XO (1 in every 2500 females)g. XYY Syndrome - an extra Y chromosome in