Genetic Control of Protein Synthesis, Cell Function, and Cell Reproduction PART 2

Cell Reproduction Mitosis is cell division Growth Cell repair Not meiosis Goal is to make identical cells Cells do not divide all the time

Mitosis is a very short period Most of the time is Interphase

Cells that cease division S phase (DNA synthesis) Genetic Control of Cell Reproduction Life Cycle of the Cell: M phase: mitosis cytokinesis Cells that cease division M (mitosis) G1 (Gap 1) G2 (Gap 2) S phase (DNA synthesis) EUKARYOTIC CELL CYCLE Interphase (>95%): G1 phase S phase (DNA synthesis) G2 phase

DNA Replication: S phase switched on by the cytoplasmic S-phase activator Replication is initiated at replication origin and proceeds in both directions. Entire genome is replicated once - further replication is blocked involves DNA polymerase and other proteins that function to unwind and stabilize the DNA and “prime” DNA replication of the “lagging” strand.

DNA Replication: S phase nucleotides are always added to the 3’ end (DNA and RNA) formation of Okazaki fragments on lagging strand “new” DNA is proofread by DNA polymerase repairs are made and gaps filled by DNA ligase

DNA Repair, “Proofreading,” and “Mutations” Following replication and prior to mitosis, DNA polymerase “proofreads” the “new” DNA, and cuts out mismatches DNA ligase replaces the mismatches with complementary nucleotides A “mistake” during transcription results in a mutation causing the formation of an abnormal protein Approximately 10 DNA mutations are passed to the next generation, however two copies of each chromosome almost always ensures the presence of a functional gene

Chromosomes and Their Replication “New” DNA helices associate with histones to form chromosomes The two chromosomes remain temporarily attached at the centromere. Together, these chromosomes are called chromatids.

Mitosis Remember PMAT Prophase Metaphase Anaphase Telophase

Interphase Technically not part of mitosis DNA is copied (duplicated) Centrosomes are duplicated

Prophase Chromosomes thicken Microtubules – mitotic spindle forming Nuclear envelope is fragmenting (prometaphase) Microtubules are attaching to kinetochore

Metaphase For middle They line up in the middle, lining up in the metaphase plate

Anaphase ”away” Chromosomes move to opposite side of the cell They have spindles Chromatids separate Equal numbers of DNA in each of the daughter cells

Telophase For two Telophase & cytokinesis Cell elongation Cleavage furrrow Daughter nuclei form

Stages of Cell Reproduction Mitosis: M phase 1. Assembly of the mitotic apparatus 2. Prophase (A,B,C) 3. Prometaphase (D) 4. Metaphase (E) 5. Anaphase (F) 6. Telophase (G, H) Figure 3-13

FILM

Cell Differentiation Different from reproduction ... changes in physical and functional properties of cells as they proliferate results not from the loss of genes but from the selective repression/expression of specific genes development occurs in large part as a result of “inductions,” one part of the body affecting another

The cell cycle & cancer Growing of cells out of control

Not all mutations lead to cancer! Dysregulation of cell growth Caused in all or almost all cases by the mutation or abnormal activation of genes that encode proteins that control cell growth and/or mitosis Proto-oncogenes: the “normal” genes Oncogenes: the “abnormal” gene Antioncogenes: genes whose product suppress the activation of oncogenes Not all mutations lead to cancer!

What causes these mutations? Ionizing radiation: disrupts DNA strands Chemicals: “carcinogens” Physical irritants: e.g., abrasion of the intestinal lining Hereditary “tendencies”: e.g., some breast cancer Viruses: so-called “tumor viruses” (particularly retroviruses)

Q: Why does cancer kill? A: Cancer cells compete successfully with normal cells for limited nutrients