Cell Cycle, DNA Replication And Mitosis

1. Cell Cycle, DNA Replication And Mitosis

2. What Did The Cell Cycle Ever Do For You? REPLICATION, DIVISION AND DIFFERENTIATION OF YOUR CELLS You began life as a fertilized egg It took many rounds of replication and division to build your many trillion-celled body In addition to replication/division making more cells, cells differentiate as they replicate, so you can develop many different tissue types

3. Your Cells Divide, Replicate And Become More Specialized With Every Cell Division In each cell type, a different subset of genes is turned on The set of genes that gets turned on determines the set of proteins the cell possesses The set of proteins the cell possesses determines the functions the cell can perform

4. What Did The Cell Cycle Ever Do For You? DEVELOPMENTALLY PROGRAMMED EVENTS SUCH AS PUBERTY REQUIRE CELLS TO KICK MITOSIS INTO HIGH GEAR EXAMPLE: GROWING BREASTS Before puberty, the breast tissue cells maintained a level of mitosis and replication/division that was enough to replace cells that got old and maintain basic tissue mass Once your body started producing estrogen, the estrogen caused the breast cells to ramp up the cell cycle and mitosis Estrogen acts as a mitogen, which is a generic term for anything that increases the rate at which cells go through the cell cycle and mitosis

5. What Did The Cell Cycle Ever Do For You? RESPONSE TO INJURY OFTEN REQUIRES NEW GROWTH IN CELLS EXAMPLE: HEALING A SKIN WOUND Before the wound, the skin cells maintained a level of mitosis and replication/division that was enough to replace cells that got old and maintain basic tissue mass Platelets release platelet-derived epidermal growth factor (PDEGF), a mitogen that acts as a paracrine hormone PDEGF causes the surrounding skin cells to ramp up the rate of cell cycle and mitosis. The skin around the wound grows and fills in the gap.

6. The Cell Cycle

7. The Cell Cycle May Also Include A G0 (G zero) Phase If DNA damage is detected, into G0 G0 If damage is reparable, the cell returns to G1 If not reparable, into apoptosis

8. The Restriction Point--Replicate Or Die

9. The Cell Checks The Phosphorylation Of Proteins Such As The Retinoblastoma Protein Cdk = cyclin-dependent kinase Kinases add phosphate groups to proteins The cell goes into apoptosis if certain proteins, example RB, are not phosphorylated

10. Tumor Suppressor Proteins Cause Potentially Cancerous Cells To Go Into Apoptosis DNA damage can cause genes that produce mitogens to continue producing them after they should have stopped The cell senses that the DNA damage is irreparable and releases the tumor suppressor protein p53 p53 stimulates production of the tumor suppressor protein p21 p21 prevents binding of the cyclins to the cyclin-dependent kinases, and prevents phosphorylation of the RB protein Because the RB protein is not phosphorylated, the cell goes into apoptosis Approx. 50% of human cancers involve mutations in the p53 gene

11. Tumor Suppressor Proteins Help Kick Potentially Cancerous Cells Into Apoptosis p53 stimulates production of p21 Cell releases p53 Cell senses that DNA damage is irreparable

12. Prokaryotic DNA's Origin Of Replication Attaches To The Cell membrane

13. DNA Replication Begins With An RNA Primer

14. DNA Polymerase Adds Nucleotides After The Primer

15. Leading Strand And Lagging Strand

16. The Lagging Strand Is Synthesized In Okazaki Fragments

17. DNA Ligase Knits The Fragments Together

18. At Each End, One Telomere Cannot Be Replicated When the telomeres get short, the cell goes into apoptosis

19. 6 Foot Long DNA Coiled Into A Microscopic Nucleus

20. Electron Micrograph Of A Metaphase Chromosome

21. Interphase To Prophase

22. Prometaphase To Metaphase

23. Anaphase To Telophase

24. Interphase Green/Yellow fibers = spindle fibers They emanate from the centrosome above the cell No discernable figures in the nucleus yet

25. Prophase Yellow dots above the nucleus are the centrosomes, beginning to move toward opposite poles of the dividing cell Light blue squiggly figures in the nucleus are the chromosomes, which are beginning to condense

26. Prometaphase Centrosomes have migrated to the poles Light blue chromosomes now obviously condensed Nuclear membrane has disappeared Spindle fibers are reaching in to bind the chromosomes

27. Metaphase Chromosomes are aligned at the equator Spindle fibers are binding the chromosomes

28. Anaphase Spindle fibers draw the chromosomes apart

29. Telophase This figure illustrates the beginning of telophase Nuclear membrane will reform Cytokinesis--cytoplasm and organelles finish streaming into the two daughter cells Cell membrane must be completed to define the new cells

30. Somatic Mutations Arise In Subpopulations Of Cells

31. Gonadal Mosaicism Can Confound Genetic Counseling A couple comes to your clinic after having a son who was affected with an X-linked disorder Because a son gets his X from his mother, you take a blood sample from Mom and test it for the presence of the mutation

32. Gonadal Mosaicism Can Confound Genetic Counseling You do not find the mutation in Mom, so you tell the couple that the risk of them having another, similarly affected, son is very low--the same as the general population’s risk. The couple has two more affected sons--What Happened?

33. Gonadal Mosaicism Can Confound Genetic Counseling Momhas what we call gonadal mosaicism Momhas a somatic mutation that arose in a cell that was destined to develop into the egg-making cells (oogonia) in her ovaries You didn’t find the mutation in Mom, because you tested her blood, and her blood cells don’t have it Depending on the percentage of her oogonia that have the mutation, all of Mom’s eggs may contain the mutation