1. How Genes are Controlled Chapter 11

2. Human Cells…. All share the same genome What makes them different????

3.  Gene regulation  turning on and off of genes  Gene expression  overall process of information flow from genes to proteins  control of gene expression allows cells to produce specific kinds of proteins  when and where they are needed How Genes are Controlled

4. Prokaryote Gene Control  Operon  cluster of genes with related functions  Contains control sequences  With few exceptions, operons only exist in prokaryotes  Proteins interacting with DNA turn prokaryotic genes on or off in response to environmental changes

5. Prokaryote Gene Control  The lactose (lac) operon includes 1.three adjacent lactose-utilization genes 2.promoter sequence where RNA polymerase binds and initiates transcription of all three lactose genes 3.operator sequence Where repressor can bind and block RNA polymerase action  regulatory gene located outside the operon codes for a repressor protein

6. When an E. coli encounters lactose, all the enzymes needed for its metabolism are made at once using the lactose operon

7. Prokaryote Gene Control In the absence of lactose: repressor binds to the operator prevents RNA polymerase action Lactose inactivates the repressor, so: operator is unblocked RNA polymerase can bind to the promoter all three genes of the operon are transcribed

9. Eukaryotic Transcription  activator proteins seem to be more important than repressors  default state for most genes seems to be off  typical plant or animal cell needs to turn on and transcribe only a small percentage of its genes

10. Eukaryotic Transcription  Eukaryotic RNA polymerase requires the assistance of proteins called transcription factors  Include: activator proteins bind to DNA sequences called enhancers and initiate gene transcription binding of the activators leads to bending of the DNA Other transcription factor proteins interact with the bound activators which then collectively bind as a complex at the gene’s promoter  RNA polymerase then attaches to the promoter and transcription begins

11. Enhancers DNA Promoter Gene Transcription factors Activator proteins Other proteins RNA polymerase Bending of DNA Transcription

12. CLONING OF PLANTS AND ANIMALS

13. Differentiated Cells  Most differentiated cells retain a full set of genes  even though only a subset may be expressed  plant cloning  root cell can divide to form an adult plant and  salamander limb regeneration  cells in the leg stump dedifferentiate, divide, and then redifferentiate, giving rise to a new leg

14. Root of carrot plant Root cells cultured in growth medium Cell division in culture Single cell Plantlet Adult plant

15. Animal Cloning using Nuclear transplantation  nucleus of an egg cell or zygote is replaced with a nucleus from an adult somatic cell  reproductive cloning  Using nuclear transplantation to produce new organisms  first used in mammals in 1997 to produce the sheep Dolly

16. The nucleus is removed from an egg cell. Donor cell A somatic cell from an adult donor is added. Nucleus from the donor cell Reproductive cloning Blastocyst The blastocyst is implanted in a surrogate mother. A clone of the donor is born. The cell grows in culture to produce an early embryo (blastocyst). Therapeutic cloning Embryonic stem cells are removed from the blastocyst and grown in culture. The stem cells are induced to form specialized cells.

17. Animal Cloning using Nuclear transplantation  embryonic stem (ES) cells  harvested from a blastocyst  Produces cell cultures for research  Produces stem cells for therapeutic treatments.

18. The nucleus is removed from an egg cell. Donor cell A somatic cell from an adult donor is added. Nucleus from the donor cell Reproductive cloning Blastocyst The blastocyst is implanted in a surrogate mother. A clone of the donor is born. The cell grows in culture to produce an early embryo (blastocyst). Therapeutic cloning Embryonic stem cells are removed from the blastocyst and grown in culture. The stem cells are induced to form specialized cells.

19. Stem Cells  Can divide indefinitely  give rise to many types of differentiated cells  Adult stem cells  give rise to many, but not all, types of cells  Embryonic stem cells  considered more promising than adult stem cells for medical applications

20. Blood cells Nerve cells Heart muscle cells Different types of differentiated cells Different culture conditions Cultured embryonic stem cells Adult stem cells in bone marrow

21. THE GENETIC BASIS OF CANCER

22. Cancer  results from mutations in genes that control cell division  Mutations in two types of genes can cause cancer 1.Oncogenes Proto-oncogenes are normal genes that promote cell division. Mutations to proto-oncogenes create cancer-causing oncogenes that often stimulate cell division. 2.Tumor-suppressor genes Tumor-suppressor genes normally inhibit cell division or function in the repair of DNA damage. Mutations inactivate the genes and allow uncontrolled division to occur.

23. Oncogene Hyperactive growth- stimulating protein in a normal amount Normal growth- stimulating protein in excess New promoter The gene is moved to a new DNA locus, under new controls Multiple copies of the gene A mutation within the gene Proto-oncogene (for a protein that stimulates cell division) DNA

24. Tumor-suppressor gene Mutated tumor-suppressor gene Normal growth- inhibiting protein Cell division under control Defective, nonfunctioning protein Cell division not under control

25. Development of Cancer  Usually four or more somatic mutations are required to produce a full-fledged cancer cell  One possible scenario is the stepwise development of colorectal cancer. 1.An oncogene arises or is activated, resulting in increased cell division in apparently normal cells in the colon lining 2.Additional DNA mutations cause the growth of a small benign tumor (polyp) in the colon wall 3.Additional mutations lead to a malignant tumor with the potential to metastasize

26. Colon wall DNA changes: Cellular changes: Growth of a polyp An oncogene is activated Increased cell division A tumor-suppressor gene is inactivated A second tumor- suppressor gene is inactivated Growth of a malignant tumor 123

27. Chromosomes 1 mutation 2 mutations 3 mutations 4 mutations Normal cell Malignant cell

28. Cancer  After heart disease, cancer is the second-leading cause of death in most industrialized nations  Cancer can run in families if  an individual inherits an oncogene or a mutant allele of a tumor-suppressor gene  most cancers cannot be associated with an inherited mutation