Mitosis and Meiosis AP BIO Study Guide Why do cells divide?

For reproduction: binary fission, asexual reproduction For growth: fertilized egg to multi-cellular organisms For repair and renewal: replace cells that die or are injured Making new cells Nucleus: chromosomes, DNA Cytoskeleton: centrioles --> organize microtubules and spindle fibers Centrosomes(animal cells only): mass of proteins that organize microtubules, guide chromosomes Getting the right stuff Exact copy of DNA, organelles, cytoplasm, cell membrane, enzymes; passed onto daughter cells Need organelles to function and carry out DNA instructions Cell cycle Interphase --> prophase --> (pro-metaphase) --> metaphase --> anaphase --> telophase/cytokinesis Interphase 90% of cells life cycle

Cell does everyday life at the same time Produce RNA, synthesize proteins/enzymes Prepares for duplication if triggered Occurs mostly in G1 stage Divided into 3 phases

G0 is just mostly a rest phase but it still does its job G1 = 1st gap/growth; prepares for division, cell grows, produces organelles, etc. S = DNA synthesis, copies chromosomes G2 = 2nd gap/growth Nucleus is well defined: DNA is loosely packed into long chromatin fibers Prepares for mitosis: replicates chromosomes, produces organelles Synthesis: dividing cell replicates DNA

Must separate DNA copies correctly to 2 daughter cells Human cell duplicates about 3 meters of DNA Error rate = about 1/1mil bases (about 30 errors per cell cycle)

Organize DNA Organized into chromosomes

Wrapped around histone proteins (thread on spools) DNA-protein complex = chromatids (long thin fiber) Condensed further in mitosis Copying and packaging After duplication, chromatid condenses

Coiling and folding to make a smaller package Mitotic Chromosomes Sister chromatids, narrow at the centromeres, contain identical copies of original DNA Mitosis Dividing cell DNA between 2 daughter nuclei Prophase:

Chromatid condenses- visible Centrioles move to opposite poles of the cell Protein fibers cross the cell to form mitotic spindle (microtubules) Nucleolus disappears and nuclear membrane breaks down Prometaphase:

Spindle fibers attach to centromere- create kinetochores Microtubules attach to kinetochores Chromosomes begin moving kinetochores Metaphase:

Chromosomes align along the middle of the cell metaphase plate Spindle fiber coordinate movement Helps ensure chromosomes separate properly Seperase breaks chromosomes into 2 chromatid Anaphase:

Sister chromatids separate at kinetochores Move to opp. poles, pulled at centromere, motor proteins walk along spindle Actin, myosin, have to use more ATP Microtubules shorten by dismantling at kinetochore end (eaten up)

Poles move farther apart Non-kinetochore microtubules lengthen Proteins holding together sister chromatids are deactivated and separate Telophase:

Chromosomes arrive at opposite poles Daughter nuclei form, nucleoli forms, chromosomes disperse (no longer visible) Spindle fibers disperse and cytokinesis begins Cytokinesis in animals:

Constriction belt of actin microfilaments squeeze around the equator of the cell Cleavage furrow forms ( )( ) Cell splits into two Cytokinesis in plants:

Cell plate forms- vesicles line up at the equator Made in the golgi- taken out by a vesicle Vesicles fuse to form 2 cell membranes New cell wall laid down between membranes (new cell wall fuses with existing) Evolution of Mitosis In eukaryotes likely evolved from binary fission in bacteria

Single circular chromosomes No membrane bound organelles Possible progression of mechanisms intermediate between binary fission and mitosis seen in modern organisms Coordination of cell division Multicellular organism, needs to coordinate division across different tissues and organs

Timing of division Rate of division Not all cells have the same cycle Frequency Varies by cell type

Embryo: cycle < 20 minutes

Skin cells: 12-24 hr. cycle Liver cells: retain ability to divide, but keep it in reserve (1-2x/year) Mature nerve cells & muscle cells dont divide after maturity- permanently at G0 Overview of cell cycle control Two irreversible points of cell cycle

Replication of genetic material (S phase) Separation of sister chromatids (anaphase) Checkpoints: process is assessed and possibly halted

Checkpoint control system Cycle controlled by stop and go chemical signals at critical points Anaphase, G1, and G2 Signals indicate if key cellular processes have completed- wait for the process to catch up Three major checkpoints G1/S phase: everyday life/duplicate chromosomes

Can synthesis begin? G2/M phase: chromosomes, organelles, committed to mitosis

Had DNA synthesis been completed correctly? Spindle checkpoint: Anaphase checkpoint

Are all chromosomes attached to spindle? Can sister chromatids separate correctly? G1/S phase: Primary decision point restriction point Whether or not its going to do its job (stop --> go to G0 phase) or divide (Go!) Internal signals: cell size, cell nutrition External signals: growth factors, nutrients G0 phase: Non-dividing differentiated state (most human cells go into G0 phase) Liver cells can go to G0 then come back out by external cues Nerve and muscle cells: highly specialized, in G0 and never divide Activation of cell division

Cell communication signals- in the cytoplasm, usually proteins (inhibitor/activator) Go-ahead signals Cyclin-dependent kinases (Cdks)

Phosphorylates- only active with cyclin Amount of cyclin changes throughout the cycle Internal signals: promoting factors (cdks) External signals: growth factors Primary mechanism of controlling protein activation phosphorylation

Cell cycle signals Cyclins-regulatory proteins, levels change throughout the cycle

Direct relationship with cdk (phosphorylatyes on/off) Cdk- complex: triggers passage through different stages of the cycle

G1/S checkpoint Cyclin D --> turns on cdk (growth factor) G2/M checkpoint MPF Protein that inhibits MPF to prevent premature M stage Spindle checkpoint Kinetochores not bound to release signal and bind APC, inhibits Cyclin peaks at anaphase Cyclin and cyclin dependent kinase Cdks and cyclin drive cell from one phase to the next Geners for these regulatory proteins have been highly conserves Basically the same in yeast, insects, plants, and animals External signals Primarily used in G1 and S phase growth factors Usually come from other cells coordination Protein signals released by body cells stimulate others to divide Density dependent inhibition: Crowded cells stop dividing, each cell binds a bit of growth factor Anchorage dependence: to divide it needs to be attached to substrate (touch sensor)

Platelet Derived Growth Factor (PDGF) Made by platelets in blood cell Promote fibroblasts Binding PDGF to cell receptors stimulates cell division in connective tissue (heals) Growth factors and cancer Growth factors can create cancers Proto-oncogenes: normally activate cell division

Become oncogenes when mutated Ex: Rts If switched on can cause a cancer Tumor: suppressor gene: normally inhibits cell division

If switched off can cause cancer Ex: p53 Cancer and cell growth Failure of cell division control Problem at G1/S checkpoint p53: protein that halts cell division if detects damaged DNA

Stimulate repair enzymes to fix DNA Force in G0 Keep in G1 arrest Cause apoptosis All cancers have to shut down apoptosis

Development of cancers Develops only after a cell experiences about 6 key mutations

Unlimited growth --> on growth promoter genes Ignore checkpoints --> off suppressor genes Escapes apoptosis --> off suicide genes Immortality = unlimited divisions --> on chromosome maintenance genes Promotes blood vessel growth --> on blood vessel growth genes Overcome anchor and density dependence --> off touch sensor gene (grow in +1 layer) Randomly occurs --> can increase mutations

Triggering cancer

Mutation in cells can be triggered by UV radiation, chemical exposure, radiation exposure, heat, cigarette smoke, pollution, age, genetics Tumors Mass of abnormal cells

Benign- stays at original site as a lump, no serious problems; can be removed by surgery Malignant- leave original site, lose attachment to nearby cells carried by blood & lymph system, start more tumors, impair functions or organs throughout body Treatment High energy radiation: kills rapidly dividing cells, can cause radiation poisoning if spread out, good for localized Chemotherapy: stop DNA replication, stop mitosis and cytokinesis, stop blood vessel growth Kill white blood cells, hair cells, and stomach cells Homologous Same genes, different alleles Autosomes carry the same genes in homologous pairs Control same inherited characteristics Meiosis Diploid haploid Fertilization restores chromosome number Meiosis I Prophase I:

Chromosomes condense Homologous chromosomes line up Synapse protein physically attaches the pairs together Crossing over occurs; switches DNA Kinetochores attach Metaphase I:

Homologous chromosomes line up on the metaphase plate Independent Assortment; random orientation of chromosomes lining up Anaphase I:

Splits homologous chromosomes apart Telophase I/Cytokinesis:

Cell splits into 2 separate cells (2n --> 1n) Meiosis II: No interphase no synthesis Separates sister chromatids Happens 2 times (for each cell) --> 4 gametes Prophase II Telophase II/Cytokinesis is exactly like mitosis Mitosis Meiosis 1 division 2 divisions Daughter cells Daughter cells Genetically identical to parent cell Genetically different to parent cell Produces 2 cells Produces 4 cells 2n --> 2n 2n --> 1n Produces cells for growth and repair Produces gametes No crossing over Crossing over Value of sexual reproduction Genetic recombination:

Crossing over Sister chromatids intertwine Homologous pairs swap pieces of chromosome NDA breaks and reattaches Very random variation 1. Cross over 2. Breakage of DNA 3. Re-fusing of DNA

Independent Assortment Offspring gametes dont have same combination of genes as parent gametes Produces 2^23 different combinations per male/female Random Fertilization Cant choose sperm/egg to create zygote (exception: test tube babies) Drives evolution provides variation for natural selection, survival of the fittest Sperm production Spermatogenesis: continuous and productive process

Quantity over quality

Egg production Oogenesis: eggs (1 million) formed when born, halt at anaphase I Quality over quantity Polar bodies are used for nutrients (not fully developed daughter cell) Meiosis II happens after fertilization