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Lecture PowerPoint to accompany Inquiry into Life Twelfth Edition Sylvia S. Mader Chapter 25 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 25.1 Control of Gene Expression • Gene Expression in Bacteria – Operon: A cluster of structural and regulatory genes that acts as a unit. • Sequences consists of: – Promoter: A sequence of DNA where transcription begins – Operator: A sequence of DNA where a repressor protein binds 25.1 Control of Gene Expression • Gene Expression in Bacteria – Example: The lac Operon in E. coli • When lactose is absent: – The regulator gene codes for a repressor that is normally active – A repressor protein binds to the operator – RNA polymerase cannot transcribe the three structural genes of the operon (the structural genes are not expressed) 25.1 Control of Gene Expression • Gene Expression in Bacteria – Example: The lac Operon in E. coli • When lactose is present: – Lactose binds with the lac repressor – Repressor is unable to bind to the operator – Structural genes are transcribed » Enzymes are produced The lac Operon 25.1 Control of Gene Expression • Gene Expression in Eukaryotes – “Housekeeping Genes” • Not finely regulated • Products are always needed to some degree 25.1 Control of Gene Expression • Gene Expression in Eukaryotes – Levels of Gene Control • Chromatin Structure • Transcriptional Control • Posttranscriptional control • Translational control • Posttranslational control 25.1 Control of Gene Expression • Levels of Gene Control – Chromatin Structure • Chromatin packing is used to keep genes turned off • Heterochromatin: inactive genes located within darkly staining portions of chromatin ex: Barr body • Euchromatin: loosely packed areas of active genes – Euchromatin still needs processing before transcription occurs – Chromatin remodeling complex pushes aside nucleosomes X-inactivation 25.1 Control of Gene Expression • Levels of Gene Control – Transcriptional Control • Most important level of control • Enhancers and promoters on DNA are involved – Transcription factors and activators are proteins which regulate these sites – Posttranscriptional Control • Removal of introns and splicing of exons • Different patterns of splicing can occur 25.1 Control of Gene Expression • Levels of Gene Control – Translational Control • Differences in the poly-A tails and/or guanine caps may determine how long a mRNA is available for translation • Specific hormones may also effect longevity of mRNA – Posttranslational Control • Some proteins must be activated after synthesis • Many proteins function only for a short time before they are degraded or destroyed by the cell Levels of Gene Control in Eukaryotes 25.1 Control of Gene Expression • Transcription Factors and Activators – Transcription Factors- proteins which help RNA polymerase bind to a promoter • Several transcription factors per gene form a transcription initiation complex – Help in pulling DNA apart and in the release of RNA polymerase for transcription – Transcription Activators- proteins which speed up transcription • Bind to an enhancer region on DNA • Enhancer and promoter may be far apart – DNA forms a loop to bring them close together Transcription Factors and Activators 25.1 Control of Gene Expression • Signaling Between Cells – Cells are in constant communication – Cell produces a signaling molecule that binds to a receptor on a target cell • Initiates a signal transduction pathway- series of reactions that change the receiving cell’s behavior – May result in stimulation of a transcription activator – Transcription activator will then turn on a gene Signal Transduction Pathway 25.2 Cancer: A Failure of Genetic Control • Contact Inhibition: When cells come into contact with neighboring cells, they stop dividing. • Cancer cells lose contact inhibition and form tumors. • The tumor is deemed noncancerous or benign if it stays as a single mass. • Cells are called cancerous when they invade surrounding tissues. • Cancer cells can travel through the bloodstream and the lymph and develop into secondary tumors. • Metastasis refers to cancer cells that have spread to other parts of the body. Development of Cancer 25.2 Cancer: A Failure of Genetic Control • Characteristics of Cancer Cells – Cancer cells are genetically unstable. – Cancer cells do not correctly regulate the cell cycle – Cancer cells escape the signals for cell death. – Cancer cells can survive and proliferate elsewhere in the body. 25.2 Cancer: A Failure of Genetic Control • Characteristics of Cancer Cells – Cancer cells are genetically unstable. • Multiple mutations, chromosome aberrations and may be present. 25.2 Cancer: A Failure of Genetic Control • Characteristics of Cancer Cells – Cancer cells do not correctly regulate the cell cycle. • Normal controls of the cell cycle do not work. • The rate of cell division and the number of cells increase. 25.2 Cancer: A Failure of Genetic Control • Characteristics of Cancer Cells – Cancer cells escape the signals for cell death. • Cancer cells do not respond to signals for apoptosis – Telomeres of cancer cells do not shorten. 25.2 Cancer: A Failure of Genetic Control • Characteristics of Cancer Cells – Cancer cells can survive and proliferate elsewhere in the body. • As a tumor grows, it stimulates the formation of new blood vessels to supply oxygen and nutrients to the cancerous cells. This is called angiogenesis. 25.2 Cancer: A Failure of Genetic Control • Proto-oncogenes and Tumor Suppressor Genes – Proto-oncogenes promote the cell cycle and prevent apoptosis. – Tumor suppressor genes inhibit the cell cycle and promote apoptosis. 25.2 Cancer: A Failure of Genetic Control • Proto-oncogenes – Mutate into cancer causing genes called oncogenes. – An altered RAS protein is found in approximately 25% of all tumors. Activity of Ras Protein 25.2 Cancer: A Failure of Genetic Control • Tumor Suppressor Genes – When these mutate, they no longer inhibit the cell cycle. – A gene called p53 normally prevents cell division if there is damage to the DNA. If p53 mutates, the cells may continue to divide indefinitely. – About 1/2 of all human cancers have a mutation in this gene. Activity of p53 Tumor Suppressor 25.2 Cancer: A Failure of Genetic Control • Causes of Cancer – Heredity • Some types of cancer run in families – Carcinogens • Environmental agents that are mutagenic • Radiation, some viruses, organic chemicals 25.2 Cancer: A Failure of Genetic Control • Diagnosis of Cancer – Screening tests • Pap smear, mammogram, colonoscopy • Tumor marker tests • Genetic tests – Confirming diagnosis • Biopsy, ultrasound, radioactive scans Needle Biopsy of the Breast 25.2 Cancer: A Failure of Genetic Control • Treatment of Cancer – Chemotherapy – Radiation therapy – Bone marrow transplant – Future Treatments • Vaccines, • Antiangiogenic drugs