Gene Control Mechanisms and Cancer Impacts

1. CHAPTER 15 Controls over Genes

2. Impacts, Issues: Between You and Eternity • Loss of gene controls can be disastrous • Some gene mutations, either inherited or spontaneously mutated due to environmental factors, predispose individuals to develop cancer • ERBB2, a type of membrane receptor, is encoded on chromosome 17 • This gene controls the cell cycle - overexpression or mutation triggers cancerous transformations

3. Impacts, Issues: Between You and Eternity • BRCA1 and BRCA2 are tumor suppressing proteins that fix damaged DNA • Breast cancer cells often contain their mutated forms

4. Between You and Eternity Fig. 15-1, p.230

5. Skin Cancer Basal Cell Carcinoma Squamous Cell Carcinoma Malignant Melanoma

6. Changes in DNA Trigger Cancer • Ultraviolet radiation can cause breaks • Can promote formation of dimers

7. Controlling the Cell Cycle • Cycle has built-in checkpoints • Proteins monitor chromosome structure, whether conditions favor division, etc. • Proteins are products of checkpoint genes • Kinases • Growth factors

8. Oncogenes • Have potential to induce cancer • Mutated forms of normal genes • Can form following insertions of viral DNA into DNA or after carcinogens change the DNA

9. Cancer Characteristics • Plasma membrane and cytoplasm altered • Cells grow and divide abnormally • Weakened capacity for adhesion • Lethal unless eradicated

10. Apoptosis • Programmed cell death • Signals unleash molecular weapons of self-destruction • Cancer cells do not commit suicide on cue

11. Bozeman Video—Gene Regulation http://www.youtube.com/watch?v=3S3ZOmleAj0

12. Gene Control Which genes are expressed in a cell depends upon: • Type of cell • Internal chemical conditions • External signals • Built-in control systems

13. Mechanisms of Gene Control Controls related to transcription Transcript-processing controls Controls over translation Post-translation controls

14. Regulatory Proteins Can exert control over gene expression through interactions with: • DNA • RNA • New polypeptide chains • Final proteins

15. Control Mechanisms • Negative control • Regulatory proteins slow down or curtail gene activity • Positive control • Regulatory proteins promote or enhance gene activities

16. Control Mechanisms • Promoters • Enhancers • Methylation and acetylation

17. Chemical Modifications • Methylation of DNA can inactivate genes • Acetylation of histones allows DNA unpacking and transcription

18. Controls in Eukaryotic Cells • Control of transcription • Transcript processing controls • Controls over translation • Controls following translation

19. Controls in Eukaryotic Cells NUCLEUS CTYOPLASM translational control protein product pre-mRNA transcript mRNA mRNA DNA transport processing control mRNA transport control mRNA degradation control protein product control transcription control inactivated mRNA inactivated protein Fig. 15-3, p.233

20. Chromosome Puff • Portion of the chromosome in which the DNA has loosened up to allow transcription • Appears in response to ecdysone • Translation of transcripts from puffed region produces protein components of saliva

21. X Chromosome Inactivation • One X inactivated in each cell of female • Creates a “mosaic” for X chromosomes • Governed by XIST gene

22. X Chromosome Inactivation • A condensed X chromosome (Barr body) in the somatic cell nucleus of a human female Fig. 15-4a, p.234

23. X Chromosome Inactivation Fig. 15-5, p.234

24. Most Genes Are Turned Off • Cells of a multicelled organism rarely use more than 5-10 percent of their genes at any given time • The remaining genes are selectively expressed

25. Phytochrome • Signaling molecule in plants • Activated by red wavelengths, inactivated by far-red wavelengths • Changes in phytochrome activity influence transcription of certain genes

26. Homeotic Genes • Occur in all eukaryotes • Master genes that control development of body parts • Encode homeodomains (regulatory proteins) • Homeobox sequence can bind to promoters and enhancers

27. Knockout Experiments • Prevent a gene’s transcription or translation • Differences between genetically engineered knockout individuals and wild-type individuals point to function of knocked out gene • Knockout experiments shed light on genes that function in Drosophila development

28. Gene Control in Prokaryotes • No nucleus separates DNA from ribosomes in cytoplasm • When nutrient supply is high, transcription is fast • Translation occurs even before mRNA transcripts are finished

29. Prokaryotic Versus Eukaryotic Gene Control

30. The Lactose Operon operator regulatory gene gene 1 gene 2 gene 3 operator transcription, translation promoter lactose operon repressor protein Fig.15-10, p. 241

31. Low Lactose • Repressor binds to operator • Binding blocks promoter • Transcription is blocked Fig.15-10, p. 241

32. High Lactose allolactose lactose mRNA RNA polymerase gene 1 operator promoter operator Fig.15-10, p. 241

33. CAP Exerts Positive Control • CAP is an activator protein • Adheres to promoter only when in complex with cAMP • Level of cAMP depends on level of glucose

34. Positive Control – High Glucose • There is little cAMP • CAP cannot be activated • The promoter is not good at binding RNA polymerase • The lactose-metabolizing genes are not transcribed very much

35. Positive Control – Low Glucose • cAMP accumulates • CAP-cAMP complex forms • Complex binds to promoter • RNA polymerase can now bind • The lactose-metabolizing genes are transcribed rapidly

36. Bozeman Video--Operons http://www.youtube.com/watch?v=10YWgqmAEsQ

37. Hormones • Signaling molecules • Stimulate or inhibit activity in target cells • Mechanism of action varies • May bind to cell surface • May enter cell and bind to regulatory proteins • May bind with enhancers in DNA

38. Polytene Chromosomes • Occur in salivary glands of midge larvae • Consist of multiple DNA molecules • Can produce multiple copies of transcripts

39. Vertebrate Hormones • Some have widespread effects • Somatotropin (growth hormone) • Others signal only certain cells at certain times • Prolactin stimulates milk production