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Inquiry into Life Eleventh Edition Sylvia S. Mader Chapter 25 Control of Gene Expression and Cancer 25-1 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 25.1 Control of gene expression • Diploid cells are totipotent – Contains all genes necessary to develop into entire organisms – Reproductive cloning shows that cells are totipotent • Reproductive cloning – Dolly the sheep- proved that animals can be cloned • Accomplished by starving an enucleated cell prior to implanting a new nucleus- forces cell into G0 • Therapeutic cloning – Produces various cell types rather than a whole organism – Provides cells and tissues to treat diseases – Allows us to gain information about differentiation 25-2 Control of gene expression cont’d. • Two methods of therapeutic cloning – Use of embryonic stem cells • Similar method as reproductive cloning • Cell is directed to become a specific cell or tissue type rather than a complete organism – Ethical considerations- each cell could have potentially become an individual – Use of adult stem cells • Many tissues have stem cells-skin, bone marrow, umbilical cord cells • Adult stem cells may not give rise to all cell types • Research is currently underway to develop techniques to allow adult stem cells to give rise to all other cell types ++25-3 Two types of cloning • Fig. 25.1 25-4 Control of gene expression cont’d. • Gene expression in bacteria – Studied in bacteria because it is simpler than eukaryotes – E. coli lac operon- all 3 enzymes for lactose metabolism are under the control of one promoter • Promoter- short DNA sequence where RNA polymerase first attaches • Three structural genes each code for an enzyme necessary for lactose metabolism • Promoter and structural genes together are called an operon 25-5 Control of gene expression cont’d. • Gene expression in bacteria cont’d. – Repression of the lac operon in E. coli • When lactose is absent in the environment, then enzymes for lactose metabolism are not necessary • Regulatory gene outside of operon codes for a repressor protein • Repressor protein binds to the promoter and prevents the structural genes from being transcribed – Induction of the lac operon in E.coli • When lactose is present it binds to repressor protein • This frees the promoter site and RNA polymerase can bond • Transcription of structural genes occurs 25-6 The lac operon • Fig. 25.2 25-7 Control of gene expression cont’d. • Gene expression in eukaryotes – Housekeeping genes- control essential metabolic enzymes or structural components that are needed all the time • Very little regulation because products are always needed – Levels of gene control • Unpacking of DNA – 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 histone 25-8 X-inactivation in mammalian females • Fig. 25.3 25-9 Control of gene expression cont’d. • Levels of gene control in eukaryotes cont’d. – Transcription • Most important level of control • Enhancers and promoters on DNA are involved – Transcription factors and activators are proteins which regulate these sites – mRNA processing • Different patterns of exon splicing – Translation • 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 25-10 Control of gene expression cont’d. • Levels of gene control in eukaryotes cont’d. – Protein activity • Some proteins must be activated after synthesis • Feedback controls regulate the activity of many proteins 25-11 Levels of gene expression control in eukaryotic cells • Fig. 25.4 25-12 Control of gene expression cont’d. • 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 must form a loop to bring them close together 25-13 Transcription factors and enhancers • Fig. 25.5 25-14 Control of gene expression cont’d. • 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 25-15 Cell-signaling pathway • Fig. 25.6 25-16 25.2 Cancer: a failure of genetic control • Characteristics of cancer cells – Form tumors • lose contact inhibition and pile on top of each other and grow in multiple layers – Lack specialization • nonspecialized and do not contribute to normal function of tissue; continue to go through the cell cycle – Abnormal nuclei • large nuclei with abnormal chromosome numbers – Spread to new locations • release a growth factor that promotes blood vessel growth, and enzymes that break down the basement membrane; cancer cells are motile and can travel in blood and lymph ++25-17 Development of cancer • Fig. 25.7 25-18 Normal cells versus cancer cells • Table 25.1 25-19 Cancer: a failure of genetic control cont’d. • Proto-oncogenes – Encode for proteins that promote the cell cycle and prevent apoptosis – Mutations in proto-oncogenes result in oncogenes that promote cell division even more than proto-oncogenes do • Results in over expression – Oncogene activity causes cell to release large amounts of cyclin • Results from mutation in cyclin-D proto-oncogene • Causes cell signaling pathway to be constantly active and prevents apoptosis – A proto-oncogene codes for a protein that makes p53 unavailable • p53 –transcription activator which stops cell cycle and promotes apoptosis 25-20 Mutations of proto-oncogenes • Fig. 25.8 25-21 Cancer: a failure of genetic control cont’d. • Tumor-suppressor genes – Mutations in tumor suppressor genes result in loss of function so products no longer inhibit cyclin nor promote apoptosis • “loss of function” mutations • Ex: retinoblastoma protein controls transcription factor for cyclin D – When tumor-suppressor gene p16 mutates, the retinoblastoma protein is always active – Cell experiences repeated replications of DNA without cell division 25-22 Mutations of tumor-suppressor genes • Fig. 25.9 25-23 Cancer: a failure of genetic control cont’d. • Other genetic changes – Telomere shortening- sequences of bases at the ends of chromosomes that keep them from fusing together • In normal cells, telomeres get shorter with each division and eventually the cell dies from apoptosis • In cancer cells, telomerase enzyme rebuilds telomeres so divisions can continue – Angiogenesis- tumor cells release growth factors that stimulate vessel and capillary growth to deliver nutrients and oxygen – Metastasis- cancer cells break through basement membranes and enter blood and lymph vessels to spread throughout body ++ 25-24 Cancer: a failure of genetic control cont’d. • Causes of cancer – Heredity • Some types of cancer run in families – Carcinogens • Environmental agents that are mutagenic, or can cause chromosomal mutations are Radiation, some viruses, organic chemicals ++ 25-25 Cancer: a failure of genetic control cont’d. • Diagnosis of cancer – Screening tests • Pap smear, mammogram, colonoscopy • Tumor marker tests • Genetic tests – Confirming diagnosis • Biopsy, ultrasound, radioactive scans • Treatment of cancer – – – – Chemotherapy Radiation therapy Bone marrow transplant Future- vaccines, anti-angiogenic drugs ++ 25-26 Cancer cells • Fig. 25.11 25-27