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PowerLecture: Chapter 15 Controls over Genes 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 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 Changes in DNA Trigger Cancer Ultraviolet radiation can cause breaks Can promote formation of dimers 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 Oncogenes Have potential to induce cancer Mutated Can forms of normal genes form following insertions of viral DNA into DNA or after carcinogens change the DNA Cancer Characteristics Plasma membrane and cytoplasm altered Cells grow and divide abnormally Weakened Lethal capacity for adhesion unless eradicated Apoptosis Programmed Signals cell death unleash molecular weapons of self-destruction Cancer cells do not commit suicide on cue Gene Control Which genes are expressed in a cell depends upon: • Type of cell • Internal chemical conditions • External signals • Built-in control systems Mechanisms of Gene Control Controls related to transcription Transcript-processing controls Controls over translation Post-translation controls Regulatory Proteins Can exert control over gene expression through interactions with: DNA RNA New polypeptide chains Final proteins Control Mechanisms Negative control Regulatory proteins slow down or curtail gene activity Positive control Regulatory proteins promote or enhance gene activities Control Mechanisms Promoters Enhancers Chemical Modifications Methylation of DNA can inactivate genes Acetylation of histones allows DNA unpacking and transcription Controls in Eukaryotic Cells Control Transcript processing controls Controls Controls of transcription over translation following translation Controls in Eukaryotic Cells NUCLEUS DNA pre-mRNA transcript transcription control CTYOPLASM translational control mRNA transport processing control mRNA mRNA transport control mRNA degradation control inactivated mRNA protein product protein product control inactivated protein Fig. 15-3, p.233 Chromosome Puff Portion of the chromosome in which the DNA has loosened up to allow transcription Translation of transcripts from puffed region produces protein components of saliva X Chromosome Inactivation One X inactivated in each cell of female Creates a “mosaic” for X chromosomes Governed by XIST gene X Chromosome Inactivation A condensed X chromosome (Barr body) in the somatic cell nucleus of a human female Fig. 15-4a, p.234 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 Phytochrome Signaling molecule in plants Activated by red wavelengths, inactivated by far-red wavelengths Changes in phytochrome activity influence transcription of certain genes petal carpel stamen sepal Fig. 15-6, p.235 B A 1 C 2 3 petals sepals 4 carpel stamens Fig. 15-6, p.235 Fig. 15-6, p.235 Fig. 15-6, p.235 Fig. 15-6, p.235 Fig. 15-6, p.235 Fig. 15-6, p.235 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 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 Knockout Experiments Fig. 15-7c, p.237 A7 A5 A3 A1 T2 T2 A8 A4 A2 T3 T1 T2 T2 Body Plan A5 A4 A6 A7 A8 A3 A2 A1 T3 T1 Lb Mx Md T2 A8 A7 A6 A4 A3 A2 A1 T3 T2 T1 A5 A4 A3 A2 A1 T3 T2 T1 A6 A7 A8 Fig. 15-8a, p.237 Body Plan Fig. 15-8b, p.237 Body Plan Fig. 15-8c, p.237 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 The Lactose Operon operator regulatory gene transcription, translation operator gene 1 gene 2 gene 3 promoter lactose operon repressor protein Fig.15-10, p. 241 High Lactose allolactose lactose mRNA operator promoter operator RNA polymerase gene 1 Fig.15-10, p. 241 Low Lactose Repressor Binding binds to operator blocks promoter Transcription is blocked Fig.15-10, p. 241 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 Positive Control – High Glucose There CAP is little cAMP cannot be activated The promoter is not good at binding RNA polymerase The lactose-metabolizing genes are not transcribed very much Positive Control – Low Glucose cAMP accumulates CAP-cAMP Complex RNA The complex forms binds to promoter polymerase can now bind lactose-metabolizing genes are transcribed rapidly 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 Polytene Chromosomes Occur in salivary glands of midge larvae Consist of multiple DNA molecules Can produce multiple copies of transcripts Vertebrate Hormones Some have widespread effects Somatotropin (growth hormone) Others signal only certain cells at certain times Prolactin stimulates milk production Fig. 15-11a, p.241 Fig. 15-11b, p.241