THE CELL CYCLE IPMAT Regulation & Its Lifespan Implication

Why Do Cells Divide?

Reproduction Reproduction –Binary Fission in bacteria Tissue Growth Tissue Growth –Growth in multicellular organisms = more cells not larger cells Tissue Repair Tissue Repair Maintain High Surface Area:Volume Maintain High Surface Area:Volume –High volume = low efficiency

Parts in the Process: Chromosomes

Parts in the Process: Centrioles & The MTOC

Parts in the Process: Spindle Fibers & Kinetochores

Parts in the Process Centrioles Centrioles –animal cells only –MT – spindle fiber organization Centrosomes Centrosomes –plant & animal cells –AKA MTOC’s

Parts in the Process Chromosomes Chromosomes –Super-coiled DNA –centromeres Spindle Fibers Spindle Fibers –MT’s attached to kinetochore –Tracks for chromosome movement toward poles

The Cell Cycle I Interphase can be divided into 3 main substages: –G 1 –G 1 – Gap 1 - period of growth –S –S – Synthesis – DNA is copied (synthesized) –G 2 –G 2 – Gap 2 – preparation for division

The Cell Cycle The Cell Cycle (continued) G 2 I Following G 2 of Interphase, mitosis (M-phase) carries out division: –P –Prophase –M –Metaphase –A –Anaphase –T –Telophase & Cytokinesis osisnotes.html

Prophase Centrosomes to poles Nuclear membrane disappears Chromatin condenses to form chromosomes

Metaphase Chromosomes in middle of cell Spindle fibers form Kinetochores attach to centromeres of each chromatid

Anaphase Sister chromatids separate Chromatids move to poles using retreating spindle fibers (D.I.)

Telophase & Cytokinesis Telophase Telophase complete division of nucleus –Spindle fibers disappear –Nuclear membranes reappear Cytokinesis Cytokinesis complete division of cytoplasm –Cleavage furrow in animals –Cell plate in plants Plant Animation Animal Mitosis

Asymmetric Division Specialization of stem cells New daughter cells not identical

Regulation of Cell Cycle G 0 Checkpoints Apoptosis –Damage Prevention –Developmental Oncogenes –Mitosis accelerators Tumor Suppressor Genes –Mitosis brakes

G 0 – Exit From the Cell Cycle temporary (wbc’s) or permanent (nerve) Cancer cells do not ever enter G 0

Checkpoints in the Cell Cycle G 1 SMcyclins kinases G 1, S, and M occur when cyclins (proteins) bind & activate kinases. Kinases phosphorylate compounds necessary for division. G 1 SM kinases blocked if damage G 1, S, or M checkpoints.

p53 ATM MAD

DNA Damage Detection G 1 G 1 –p53 –p53, a tumor suppressor, checks for damage before DNA replication –If damage cannot be repaired, p53 sends cell to to die so it cannot lead to cancer –P53 mutations implicated in > ½ of all human cancers S –ATM –ATM detects DNA damage, helps p53 send irreparably damaged cells to death, & maintains telomere length M –MAD –MAD stops mitosis if problems w/ microtubles in spindle fiber formation

Definition Mechanism of normal, controlled death by: –DNA fragmentation –Cytoplasm shrinkage –Membrane blebbing Cellular “suicide” No spillage or damage to nearby cells No inflammatory response ml

Is All Cell Death Equal? Necrosis –Messy cell death usually due to injury –Cellular “homicide” –Cell contents come spilling out leading to an inflammatory response. Swelling Redness Fever

Why Suicide? Development –Mouse paws (and human hands) use cell death to form digits.

Death As A Necessity For Life Immune system cells Virally infected cells Immune cells that don’t recognize “self” Removal of cytotoxic T cells after infection is conquered DNA damaged cells Sent to their death by p53 to prevent tumors

Disorders Involved Neurological disorders such as Huntington’s, Parkinson’s and Alzheimer’s diseases Too much apoptosis Cancer Not enough apoptosis Cell DivisionCell Death

Genes in Cancer Oncogenes Oncogenes –Genes known to speed up mitosis –Mitosis accelerators when ON (phosphorylation) –Cancer results if ON when should be OFF Tumor Suppressor Genes Tumor Suppressor Genes –Mitosis brakes –Tumors result if OFF when should be ON

Can a Cell Divide Forever? Normal CellsNO Normal Cells – NO –Telomeres –Telomeres, buffer tips of each chromosome, get shorter w/ each division –Cells die when telomeres gone EX: Aging effects are due to dead cells that can no longer be replaced

Can a Cell Divide Forever? Cancer CellsYES Cancer Cells – YES –Telomerase is ON Enzyme repairs telomeres after each division Embryonic Stem CellsYES Embryonic Stem Cells – YES –Fountain of Youth lies in harnessing anti- aging powers of telomerase w/o risk of cancer NO EASY TASK

The Cell Cycle