When DNA Can't Be fixed

1. Changes in DNA are triggers for skin cancer, like the most deadly type--malignant melanoma.



2. Cancers are malignant forms of tumors.
   
   
   1. Tumors are tissue masses that arise through mutations in the genes that govern growth and division.
   
   
   
   2. Malignant tumors grow rapidly, causing destructive effects on surrounding cells.


3. Gene controls are molecular mechanisms that govern when and how fast specific genes will be transcribed and translated.

15.1   Types of Control Mechanisms

1. Because all cells in your body have the same genetic instructions, only a relatively small number of genes are active at any given time in any given tissue.
   
   
   1. Which genes are expressed depends on the type of cell, its responses to chemical signals, and built-in control systems.
   
   
   
   2. Regulatory proteins interact with DNA, RNA, or actual gene products.


2. Several control systems are used by cells:
   
   
   1. In negative control, a regulatory protein binds to the DNA to block transcription; it can be removed by an inducer.
   
   
   
   2. In positive control, a regulatory proteins binds to the DNA and promotes initiation of transcription.
   
   
   
   3. In chemical modification, regions of newly replicated DNA can be shut down by methylation and access to genes can be controlled by acetylation of histone proteins that organize DNA.

15.2   Bacterial Control of Transcription

1. Negative Control of the Lactose Operon
   
   
   1. E. coli bacteria (common in the human digestive tract) can metabolize lactose because of a series of genes that code for lactose-digesting enzymes.
      
      
      1. The three genes are preceded by a promoter and an operator--all together called an operon.
      
      
      
      2. A regulator gene nearby codes for a repressor protein that binds to the operator when lactose concentrations are low and effectively blocks RNA polymerase's access to the promoter.
   
   
   2. When milk is consumed, the lactose binds to the repressor changing its shape and effectively removing its blockage of the promoter; thus RNA polymerase can now initiate transcription of the genes.


2. Positive Control of the Lactose Operon
   
   
   1. The lactose operon also is subject to positive control by an activator protein called CAP.
      
      
      1. RNA polymerase will bind to the promoter if CAP is already there.
      
      
      
      2. And in turn, CAP must first be activated by cAMP.
   
   
   2. When glucose is scarce, the CAP-cAMP complex forms and turns on the lactose-metabolism genes.

15.3   Gene Controls in Eukaryotic Cells

1. Much less is known about gene controls in multicelled eukaryotes because patterns of gene expression vary within and between body tissues.



2. Cell Differentiation and Selective Gene Expression
   
   
   1. All body cells have the same genes, but the cells of different tissues are differentiated (specialized) because of selective gene expression.
   
   
   
   2. Controls related to transcription include: gene amplification (more replicates of DNA); DNA rearrangements (cutting and splicing of DNA segments); and chemical modifications (histone interactions).
   
   
   
   3. Post-transcriptional controls include: transcript processing (introns and exons); transport controls (dictate which mature transcripts will be shipped to the cytoplasm for translation); and post-translational controls (govern the modifications to polypeptides).

15.4   Types of Control Mechanisms

1. Homeotic Genes and Body Plans
   
   
   1. Homeotic genes interact with one another and with control elements to bring about the formation of tissues and organs in accordance with the basic body plan.
   
   
   
   2. These genes code for regulatory proteins that can bind to promoters and enhancers to control transcription.


2. X Chromosome Inactivation
   
   
   1. In mammalian females, the gene products of only one X chromosome are needed; the other is condensed and inactive--called a Barr body.
   
   
   
   2. Because in some cells the paternal X chromosome is inactivated, while in other cells the maternal X chromosome is inactivated, each adult female is a mosaic of X-linked traits, called mosaic tissue effect.
   
   
   
   3. This mosaic effect is seen in human females affected by anhidrotic ectodermal dysplasia in which a mutant gene on one X chromosome results in patches of skin with no sweat glands.

15.5   Examples of Signaling Mechanisms

1. Hormone Signals
   
   
   1. Hormones are major signaling molecules that can stimulate or inhibit gene activity in target cells.
      
      
      1. Some hormones bind to membrane receptors on cell surfaces.
      
      
      
      2. Others enter cells to bind with regulatory proteins to initiate transcription, often with the aid of enhancer sequences.
   
   
   2. In the salivary glands of insect larvae, the polytene chromosomes respond to the hormone ecdysone by puffing out during transcription.
   
   
   
   3. In vertebrates, some hormones such as somatotropin have widespread effects because most of the body's cells have receptors for it; whereas, prolactin affects only the mammary glands because only they have the receptors.


2. Sunlight as a Signal
   
   
   1. Plant seedlings will respond to a single burst of light by making chlorophyll.
   
   
   
   2. Phytochrome is a blue-green pigment that helps plants adapt to the changing light conditions of day/night and seasons by signaling genes responsible for germination, stem elongation, branching, leaf expansion, and formation of flowers, fruits, and seeds.

15.6   Focus on Science: Lost Controls and Cancer

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