DNA Repair and Human Disease (Medical Intelligence Unit)

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Moreover, in the last decade or so, researchers have succeeded in identifying many of the genes and even mutations that are responsible for specific genetic diseases. Now scientists have found ways of identifying and isolating genes that have specific biological functions and placing those genes in another organism, such as a bacterium, which can be easily grown in culture. With these techniques, known as recombinant DNA technology , the ability to cure many serious genetic diseases appears to be within our grasp.

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Isolating the specific gene or genes that cause a particular genetic disease is a monumental task. Thus, the first task is to obtain smaller pieces of DNA that can be more easily handled. Fortunately, researchers are able to use restriction enzymes also known as restriction endonucleases , discovered in , which are enzymes that cut DNA at specific, known nucleotide sequences, yielding DNA fragments of shorter length.

For example, the restriction enzyme EcoRI recognizes the nucleotide sequence shown here and cuts both DNA strands as indicated:. Once a DNA strand has been fragmented, it must be cloned; that is, multiple identical copies of each DNA fragment are produced to make sure there are sufficient amounts of each to detect and manipulate in the laboratory.

Cloning is accomplished by inserting the individual DNA fragments into phages bacterial viruses that can enter bacterial cells and be replicated. When a bacterial cell infected by the modified phage is placed in an appropriate culture medium, it forms a colony of cells, all containing copies of the original DNA fragment. This technique is used to produce many bacterial colonies, each containing a different DNA fragment. The result is a DNA library , a collection of bacterial colonies that together contain the entire genome of a particular organism. The next task is to screen the DNA library to determine which bacterial colony or colonies has incorporated the DNA fragment containing the desired gene.

One way is to use a segment of the desired gene isolated from another organism. An alternative method depends on knowing all or part of the amino acid sequence of the protein produced by the gene of interest: the amino acid sequence is used to produce an approximate genetic code for the gene, and this nucleotide sequence is then produced synthetically. The amino acid sequence used is carefully chosen to include, if possible, many amino acids such as methionine and tryptophan, which have only a single codon each.

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After a probe identifies a colony containing the desired gene, the DNA fragment is clipped out, again using restriction enzymes, and spliced into another replicating entity, usually a plasmid. Plasmids are tiny mini-chromosomes found in many bacteria, such as Escherichia coli E. A recombined plasmid would then be inserted into the host organism usually the bacterium E.

Proponents of recombinant DNA research are excited about its great potential benefits. An example is the production of human growth hormone, which is used to treat children who fail to grow properly. Formerly, human growth hormone was available only in tiny amounts obtained from cadavers. Now it is readily available through recombinant DNA technology. Another gene that has been cloned is the gene for epidermal growth factor, which stimulates the growth of skin cells and can be used to speed the healing of burns and other skin wounds.

In addition to advancements in the ongoing treatment of genetic diseases, recombinant DNA technology may actually lead to cures. When appropriate genes are successfully inserted into E. Recent accomplishments include the production in E. Scientists have used other bacteria besides E. Plant molecular biologists use a bacterial plasmid to introduce genes for several foreign proteins including animal proteins into plants.

The bacterium is Agrobacterium tumefaciens , which can cause tumors in many plants, but which can be treated so that its tumor-causing ability is eliminated. Restriction enzymes have been isolated from a number of bacteria and are named after the bacterium of origin. EcoRI is a restriction enzyme obtained from the R strain of E. The roman numeral I indicates that it was the first restriction enzyme obtained from this strain of bacteria. For each genetic disease, indicate which enzyme is lacking or defective and the characteristic symptoms of the disease.

Skills to Develop To describe the causes of genetic mutations and how they lead to genetic diseases. Summary The nucleotide sequence in DNA may be modified either spontaneously or from exposure to heat, radiation, or certain chemicals and can lead to mutations. Mutagens are the chemical or physical agents that cause mutations. Genetic diseases are hereditary diseases that occur because of a mutation in a critical gene. Is UV radiation an example of a physical mutagen or a chemical mutagen? What causes PKU?

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Now, the basic research of the mechanisms of DNA repair is merging with clinical research, placing the action of the DNA repair pathways in the context of the whole organism. Such integrative approach ena Such integrative approach enables understanding of the disease mechanisms and is invaluable in improving diagnostics and prevention, as well as designing better therapies.

This book highlights the central role of DNA repair in human health and well-being. The reviews presented here, contain detailed descriptions of DNA repair pathways, as well as analysis of a large body of evidence addressing links between DNA damage repair and human health. They will be of interest to a broad audience, from molecular biologists working on DNA repair in any model system, to medical researchers.

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