A.  Chapter Summary

     Gene mutations are changes in the structure of DNA that alter a gene. There are four different kinds of gene mutations that affect the amino acid sequence. A missense mutation is when a base substitution changes a single amino acid in a polypeptide sequence. A silent mutation does not alter the amino acid sequence of the polypeptide, even though the nucleotide sequence is changed. A nonsense mutation involves a change from a normal codon to a stop or termination codon. A frameshift mutation involves the addition or deletion of nucleotides that are not in multiples of three nucleotides. Any of these mutations can occur anywhere in the gene, not only in the coding sequence. Depending on what part of the gene the mutation is in, it may cause different results. Mutations can occur in germ-line cells or somatic cells. Germ-line cells are cells that give rise to gametes, such as egg and sperm cells. If there is a mutation in a germ-line cell it affects the entire body and is passed on to offspring. Somatic cells are every other cell in the body besides germ-line cells.  A mutation in a somatic cell only affects part of your body. If the mutation arises earlier in development, than the patch is larger, whereas if it arises later in development the patch is smaller. Mutations may be either spontaneous or induced. Spontaneous mutations result from abnormalities in biological processes; such as enzymes that function improperly or toxic chemicals produced by metabolic processes. Induced mutations are caused by environmental agents that enter the cell and alter the structure of DNA. Another name for the environmental agents that cause mutations is mutagens. Mutagens can be either chemical or physical and they affect DNA structure by covalently modifying the structure of nucleotides or altering DNA replication. The Ames test uses a strain of a bacterium, Salmonella typhimurium, to tell if a substance is a mutagen or not.

     The body has three DNA repair systems; direct repair, base excision (BER) and nucleotide excision repair (NER), and methyl-directed mismatch repair. Direct repair is when a repair enzyme recognizes an incorrect structure in the DNA and directly converts it back to a correct structure. BER and NER is when an abnormal base or nucleotide is recognized, and a portion of the strand containing the abnormality is removed. The complementary DNA strand is then used as a template to synthesize a normal DNA strand. NER is used to UV-induced damage, chemically modified bases, missing bases, and various types of cross-links (such as thymine dimers). Methyl-directed mismatch repair is similar to excision repair except that the DNA defect is a base pair mismatch in the DNA not an abnormal nucleotide.

            If one of these repair systems does not fix the mutation than the result is usually cancer. Cancer is a disease caused by a mutation in a gene that results in uncontrolled cell division. Only 10% of cancers are genetic. Cancers typically arise from single cell that through generations, has undergone a series of mutations. The one cell divides way too much and causes a tumor to form. The tumor is first often benign, meaning that it is not harmful. However if more mutations occur it could become malignant, which means that it is then considered cancerous. Soon the cancer cells start to spread throughout the body through blood and bodily fluids through a process called metastasis. Metastasis is extremely dangerous because if you completely take a tumor out of one area of the body because of metastasis another one might pop up somewhere else.

B.  Useful Materials

This video is a song about a single cell that has a mutation. It doesn't respond to the checkpoints so it divides uncontrollably. The song actually is a little informational. It also has good graphics that go along with the words. The lyrics are also at the bottom of the screen in case you can't understand what they are saying. 

Added: 2/6/11 Source: Youtube

This video is a short virtual lecture about frameshift mutations. A frameshift mutation is when an amino acid is either deleted or added to the DNA sequence. This is one of the four main kinds of gene mutations discussed in section 1 Mutations. In the video, the narrator guy shows what would happen if one, two, or three amino acids were added to a DNA sequence.

Added:2/6/11 Source: Youtube

New Discovered DNA Repair Mechanism

The new discovered DNA repair mechanism fixes bases that have been akylated. Instead of cutting the section out, or replacing it, it is flipped to the opposite side. This kind of DNA repair is more common in bacteria than in eukaryotes

Added:2/6/11 Source:ScienceDaily

Restoring Expression of wild-type p53 suppresses tumor growth but does not cause tumor regression in mice with a p53 missense mutation.

     Many cancers are caused by mutations in the P53 gene. However, over  80% of the P53 mutations found in human cancers are missense mutations that lead to expression of mutant proteins that not only lack p53 transcriptional activity but exhibit new functions as well. Recent studies show that restoration of p53 expression leads to tumor regression in mice carrying p53 deletions. In this experiment, they show that restoring wild-type p53 expression halted tumor growth in mice inheriting a p53R172H missense mutation that is equivalent to a p53 missense mutation detected in approximately 6% of human cancers. However, it did not lead to tumor regression, as was observed in mice lacking p53. The results of this experiment show that restoring wild-type p53 expression is definitely beneficial in treating human cancers caused by missense mutations is the p53 gene, however there is more work to be done. This article applies to what we learned in class because both p53 and missense mutations are mentioned in section 3 about cancers.

Added:2/6/10 Source: PubMed