THE CELL CYCLE AND CELL DIVISION CHAPTER 11 Lecture Objectives  How Do Prokaryotic and Eukaryotic Cells Divide?  How Is Eukaryotic Cell Division Controlled?  What Happens During Mitosis?  What Role Does Cell Division Play in a Sexual Life Cycle?  What Happens During Meiosis?  In a Living Organism, How Do Cells Die?  How Does Unregulated Cell Division Lead to Cancer?

Why is cell division important? Signal

Events in cell division

DNA duplication Segregation Cytokinesis Binary fission (prokaryotes) Cell division in eukaryotes Signals for cell division are related to the needs of the entire organism. Many chromosomes; replication and segregation are more intricate. DNA replication occurs between cell divisions Sister chromatids—newly replicated chromosomes are closely associated. Mitosis & meiosis Mitosis separates them into two new nuclei, identical to the parent cell. Meiosis is nuclear division in cells involved in sexual reproduction. The cells resulting from meiosis are not identical to the parent cells.

The eukaryotic cell cycle Parts of the cell cycle

G1 S G2 Restriction points M and Cytokinesis What regulates the cell cycle

Signals that control cell division Cyclin-dependant kinases (cdk’s) Cdk is activated by binding to cyclin The G1-S cyclin-Cdk complex acts as a protein kinase and triggers transition from G1 to S Other cyclin-Cdk’s act at different stages of the cell cycle Cdk’s-cyclin complex Retinoblastoma Progress past the restriction point in G1 depends on retinoblastoma protein (RB). RB normally inhibits the cell cycle, but when phosphorylated by G1-S cyclin-Cdk, RB becomes inactive and no longer blocks the cell cycle. How cdks-cyclin complex controls cell cycle Cyclins are transient during cell cycle Cyclin-Cdk’s act at cell cycle checkpoints to regulate progress. Example: If DNA is damaged during G1, p21 protein is made. p21 binds to G1 Cdk’s, preventing their activation. The cell cycle stops while DNA is repaired Factors affecting cell division Growth factors (platelet-derived growth factor) Interleukins Erythropoietin

Chromatin, chromosomes, chromatid DNA molecules are extensively “packed” even during interphase. Histones Nucleosomes. Dna densely packed Dna in mitosis Segregation The centrosome determines the plane of cell division It doubles during S phase and will determine the spindle orientation Each centrosome can consist of two centrioles—hollow tubes formed by microtubules— at right angles The centrosomes move to opposite ends of the nuclear envelope during G2-to-M transition. Tubulin dimers surrounds the centrosomes. Tubulin proteins initiate formation of microtubules, which leads to formation of the spindle structure. Plant cells lack centrosomes but have distinct microtubule organizing centers

Prophase Prometaphase Metaphase Anaphase Telophase Mitotic spindle Phase of mitosis

Mitosis

Sister chromatids Cytokinesis differs in animal & plants Asexual reproduction (clones) Sexual reproduction Gametes Offspring genetically different from parents Somatic cells vs gametes Haploid vs Diploid Homologous chromosomes Fertilization (zygote) Haplontic life Alternation of generation Diplontic life Karyotype Meiosis How diplontic life makes gametes Reduction in the number of chromosomes Genetic diversity

Genetic recombination during cross over Crossing over Prophase I may last a long time. Human males: Prophase I last about 1 week, and 1 month for entire meiotic cycle Human females: Prophase I begins before birth, and ends up to decades later during the monthly ovarian cycle

MEIOTIC ERRORS NONDISJUNCTION TRANSLOCATION

ANEUPLOIDY & pOLYPLOIDY

Polyploidy (e.g., 3n) can prevent meiosis because not all chromosomes will have a homolog, and anaphase I will not take place. Polypolidy can enhance crop plants and triploidy produces sterile trout to stock rivers. Conditions of aneuploidy Down syndrome Miscarriages Cell death Necrosis

Apoptosis Events in apoptosis Cell detaches from its neighbors Cuts up its chromatin into nucleosome-sized pieces Forms membranous lobes called “blebs” that break into fragments Surrounding living cells ingest the remains of the dead cell Cell death cycle is controlled by signals: Lack of a mitotic signal (growth factor) Recognition of damaged DNA External signals cause membrane proteins to change shape and activate enzymes called caspases—hydrolyze proteins of membranes. apoptosis cancer Benign tumors

Malignant tumors Metastasis A cancer cell and normal cells around it There are factors that increase (positive) cell division (growth factors) Some inhibit (negative) cell division (RB) Oncogenes: positive regulator Example: HER2 gene in breast cancer Tumor Suppressors: negative regulators (p21, p53, RB) may be blocked by the HPV Molecular changes in cancer cells (positive) Molecular changes in cancer cells (negative) Cancer treatment targets the cell cycle and tries to inhibit division Drugs such as 5-flourouracil block thymine, a base of DNA. Taxol interferes with the mitotic spindle. Herceptin targets only the HER2 growth factor receptor in some breast cancers. Cancer treatment interferes with cell cycle of cancer cell