Essentials of BiologySylvia S. Mader

Chapter 12Lecture Outline

Prepared by: Dr. Stephen EbbsSouthern Illinois University Carbondale

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

12.1 Control of Gene Expression

• The cell cycle and DNA replication ensure that every cell receives a complete copy of all chromosomes and their genes.

• Each somatic (body) cell therefore has the capacity to become a complete organism.

• This information can be used in cloning.

Reproductive and Therapeutic Cloning

• Reproductive cloning involves the production of an individual genetically identical to the original individual.

• This type of cloning is easy to do with plants.

• Reproductive cloning of animals is more difficult.

Reproductive and Therapeutic Cloning (cont.)

Reproductive and Therapeutic Cloning (cont.)

Reproductive and Therapeutic Cloning (cont.)

• Therapeutic cloning is used to produce mature cells of specific cell types.

• There are two main purposes for therapeutic cloning.– This type of cloning provides information

about how specialization of cells occurs.– The cells provided by therapeutic cloning can

be used to treat diseases of specific organs.

Reproductive and Therapeutic Cloning (cont.)

Reproductive and Therapeutic Cloning (cont.)

• There are two strategies for conducting therapeutic cloning.– Use reproductive cloning with embryonic stem

cells– Use adult stem cells

Mechanisms of Gene Expression

• Not all genes in a cell are used to accomplish its given functions.

• Specialized cells (nerve, muscle, gland) use only some of the genes, which makes each cell type distinct.

• The selective activity of certain genes is a highly regulated process called gene expression.

Mechanisms of Gene Expression (cont.)

Gene Expression in Prokaryotes

• In prokaryotic cells, groups of genes involved in a related function are controlled by a single promoter.

• This group of genes and its promoter is called an operon.

• An example is the lac operon in E. coli, which has genes for lactose metabolism.

Gene Expression in Prokaryotes (cont.)

• The activity of the lac operon is controlled by a repressor protein encoded by a regulatory gene.

• The repressor binds to a site in the operon called the operator.

• When bound to the operator, the gene is inactive because RNA polymerase can’t bind to synthesize mRNA.

Gene Expression in Prokaryotes (cont.)

• Lactose can bind to the repressor, preventing it from binding to the operator.

• RNA polymerase is now free to bind to the operon promoter and synthesize mRNA.

• The tryptophan (trp) operon operates in a similar manner.

Gene Expression in Prokaryotes (cont.)

Gene Expression in Prokaryotes (cont.)

Gene Expression in Eukaryotes

• In eukaryotes, the control of gene expression involves several mechanisms at different levels.– DNA unpacking in the nucleus– Transcription in the nucleus– mRNA processing in the nucleus– Translation in the cytoplasm– Protein activity in the cytoplasm

Gene Expression in Eukaryotes (cont.)

DNA Unpacking

• In eukaryotes, the packing of DNA into chromatin can prevent some genes from being expressed.

• Inactive genes can be located in the heterochromatin.

• One example of heterochromatin is the X-chromosome Barr body.

DNA Unpacking (cont.)

DNA Unpacking (cont.)

• Active genes are associated with more loosely packed chromatin called euchromatin.

• To transcribe a gene within the euchromatin, a transcription activator is required.

DNA Unpacking (cont.)

mRNA Processing

• During mRNA processing, the introns are removed and the exons spliced to form a mature mRNA.

• The splicing of exons can be different for the same gene in different cells, producing a different mature mRNA.

• These different mRNA produce different proteins.

Transcription Factors and Transcription Activators (cont.)

• Transcription activators are proteins that speed the rate of transcription.

• Transcription activators bind to a DNA region called the enhancer.

• Transcription is enhanced when the transcription activators, transcription factors, and RNA polymerase are brought together.

Transcription Factors and Transcription Activators (cont.)

Signaling Between Cells

• Cells in living organisms continually communicate with each other with signals.

• These signals can control activity of cells.

• This control requires a cell-signaling pathway in order to operate.

mRNA Processing (cont.)

Translation of mRNA

• The translation of mRNA by ribosomes in the cytoplasm is controlled by other proteins.

• For example, initiation factor IF-2 inhibits protein synthesis when phosphorylated.

Protein Activity

• Some proteins are not immediately active after their synthesis is complete.

• For example, insulin must have a short sequence of amino acids removed before it can assume its proper tertiary structure.

• Proteosomes may also regulate protein activity by degrading proteins that are no longer needed.

Protein Activity (cont.)

Transcription Factors and Transcription Activators

• Transcription of individual genes in eukaryotes can be controlled by several different proteins.

• The group of proteins that control the initiation of transcription are called transcription factors.

• These transcription factors are organized as the transcription activation complex.

Signaling Between Cells (cont.)

• A cell-signaling pathway begins when a signal binds to a receptor on the target cell’s plasma membrane.

• Once bound, the signal induces a signal transduction pathway.

• This pathway then initiates the responses to the signal, such as gene transcription.

Signaling Between Cells (cont.)

12.2 Cancer: A Failure of Genetic Control

• Cancer is a genetic disease caused by a series of mutations.

• The mutations must disrupt the regulatory pathways that control cell division to cause cancer.

• Cancer cells therefore have characteristics different from normal cells.

12.2 Cancer: A Failure of Genetic Control (cont.)

12.2 Cancer: A Failure of Genetic Control (cont.)

• Fibroblasts and adult stem cells are the types of cells that can become cancerous.

• Cancerous cells also release chemicals to enhance the progression of the cancer.

12.2 Cancer: A Failure of Genetic Control (cont.)

12.2 Cancer: A Failure of Genetic Control (cont.)

12.2 Cancer: A Failure of Genetic Control (cont.)

12.2 Cancer: A Failure of Genetic Control (cont.)

12.2 Cancer: A Failure of Genetic Control (cont.)

Cancer Is a Genetic Disease

• Cancer occurs because the cell cycle occurs uncontrollably.

• The loss of control of the cell cycle is the result of mutations in two types of genes.– The proto-oncogenes code for proteins

promote the cell cycle and prevent apoptosis.– The tumor suppressor genes inhibit the cell

cycle and stimulate apoptosis.

Cancer is a Genetic Disease (cont.)

Proto-Oncogenes Become Oncogenes

• Cancer-causing genes called oncogenes are created when a mutation occurs in a proto-oncogene.

• This is a gain-of-function mutation because the oncogenes are more active than the proto-oncogenes.

• For example, some oncogenes code for the Ras proteins, which stimulate the cell cycle by activating cyclin.

Tumor Suppressor Genes Become Inactive

• Mutations in tumor suppression genes remove the products that control the cell cycle or stimulate apoptosis.

• These are loss-of-function mutations.

• For example, when the tumor suppressor gene p16 mutates, retinoblastoma protein is continually functional and results in too much active cyclin.

Tumor Suppressor Genes Become Inactive (cont.)

Other Genetic Changes

• Cancer cells undergo additional genetic changes that result in specific characteristics.

Absence of Telomere Shortening

• The cell’s telomeres shorten with the completion of each cycle of cell division.

• Telomere length determines the longevity of the cell’s life span.

• In cancer cells, an enzyme called telomerase is activated which rebuilds the telomere.

Angiogenesis

• During angiogenesis, new blood vessels form to provide blood to cancerous tumors.

• The vascular endothelial growth factor is released by cancer cells to stimulate angiogenesis.

• The drugs angiostatin and endostatin are used to treat cancer by inhibiting angiogenesis.

Metastasis

• If a tumor is benign, it does not invade neighboring tissues.

• Cancer in situ is located in its place of origin before any invasion of neighboring tissue.

Metastasis (cont.)

Metastasis (cont.)

• A tumor is malignant if it undergoes metastasis and spreads to establish new tumors in other parts of the body.

• The mobility of cancer cells in the body is enhanced by mutations that affect the cell cytoskeleton.

Hereditary Forms of Cancer

• Environmental influences such as radiation, chemicals, and viruses are risk factors for the development of cancer.

• A predisposition to certain cancers can also be hereditary.

Inheritance Patterns for Cancer

• A predisposition to some cancers occurs when an individual has autosomal recessive alleles of tumor suppression genes.

• Other cancers can be caused by the presence of autosomal dominant genes.

Testing for These and Other Genes

• Genetic tests have been developed to identify mutant alleles genes associated with cancer.– The BRCA, RET, and RB genes– The ras oncogene

• Tests are also available to determine if the enzyme telomerase is active in cells.