Chapter 14 Gene Control

--in multicellular organisms, only 5-10% of the genes are on in any given cell. All cells have same DNA, but which genes are on determines the type of cell it is and what that cell can do.

--mostly, a gene being regulated means whether it is transcribed into RNA or not. The processes after that: RNA processing, transport to cytoplasm, translation, modification after translation--are mostly automatic (but sometimes regulation can occur at any of these steps).

--a simple form of regulation, the paradigm for the whole subject: the lac operon in E. coli. Escherichia coli is a common gut bacterium. Some forms of it (sub-species) cause food poisoning, but most are harmless.

--Prefers glucose as food--the basic sugar at the start of all metabolic processes. But, if no glucose is present, it will live happily on lactose, milk sugar, which is a disaccharide composed of a glucose plus galactose (another simple sugar very similar to glucose).

--B-gal is only needed when lactose is present. It is a waste of energy to make it when there is no lactose around. So, the lac gene is shut off when there is no lactose around.

--recall that gene transcription starts when RNA polymerase attaches to the promoter region at the start of the gene. The RNA polymerase then moves down the gene, creating an RNA copy (mRNA) of the gene until it reaches the end. The lac gene is regulated by preventing RNA polymerase from attaching to the promoter.

--between the promoter and the gene is another DNA sequence, the operator. The actual control occurs at the operator.

--the key regulator is another protein, the lac repressor. It is made by another gene, at all times and at a low rate. The lac repressor can bind to 2 different things, but not simultaneously: it can either bind to the operator, in which case RNA polymerase can't get to the promoter, and the gene is off because transcription can't occur if RNA polymerase doesn't bind to the promoter. Or, it can bind to lactose. If the repressor binds to lactose, it can't bind to the operator, so the RNA polymerase can bind to the promoter and the gene is on, it is transcribed.

--the repressor protein prefers binding to lactose. So, if the repressor is bound to the operator and lactose appears, the repressor leaves the operator and binds to lactose instead. Thus, if to add lactose to the cell, the lac gene gets turned on. However, if the amount of lactose gets too low, there will be some repressor proteins with no lactose to bind it, so they will bind to the lac gene operator instead, turning it off.

--lac gene regulation is negative control: the gene would be on all by itself, and the repressor protein turns it off. Many genes have positive control instead: off normally, but turned on by specific proteins. This is positive control, much more common in eukaryotes.

--cancer is caused by mutations in gene control mechanisms. Lots of different kinds, and we don't have a complete list yet at all. Genes that cause cancer when mutated are called oncogenes. There are several hundred oncogenes: they all have important functions in the cell when not mutated.

--An example: the sis oncogene normally makes a protein called platelet-derived growth factor: causes skin cells to grow and divide, to heal wounds, for example. PDGF is secreted by platelets, blood cells involved in clotting. The skin cells respond to PDGF because they have a receptor for it on their cell surface: when PDGF binds to the receptor, the skin cells start to divide.

--Skin cells make the receptor protein and platelets make the PDGF. However, in certain forms of skin cancer, the PDGF gene (sis) is mutated so as to turn it on in the skin cells. These mutated cells now have both the receptor and the stimulus (the PDGF). They get into a feedback loop: the more PDGF they make, the more they divide in response to it, and in turn the cells make still more PDGF: uncontrolled cell division = cancer.

--lots of forms of cancer are like this, but mostly occur completely within the cell: this one is unusual because the PDGF is actually secreted and responded to as if it were an outside stimulus.