A.  Daily Blog

A mutation is a heritable change in the DNA and are essential to life.  Mutations are what have caused Homo sapiens to evolve into what we are today, therefore mutations aren't always bad.  However, it is important to know that they are more often harmful than beneficial.  Cancer is a disease caused by a series of mutations.

 

There are different types of mutations.  Silent mutations do not alter the amino acid sequence.  Missense mutations change one amino acid in a polypeptide chain.  Nonsense mutations change a normal codon into a start or stop codon.  Lastly, frameshift mutations are when nucleotides that are not multiples of three are deleted or added.  Basically, mutations can really mess up the functions of proteins and the DNA.  It is important to know that germ-line mutations are heritable while somatic mutations are not.  (Germ-line refers to gametes while somatic refers to all of our other cells.)

 

Also, mutations can be spontaneous or induced.  They are true to their respective names.  Spontaneous mutations are due to abnormalities in the biological process, while induced mutations are caused by environmental agents.  The chemical or physical agents that bring about induced mutations are called mutagens.  

 

DNA repair is a very important response to damage to the DNA because if damaged DNA is not repaired, then defective cells would proliferate, thus leading up to cancer.  DNA repair is a two prong process.  First the damage must be detected and then it must be fixed.  If one of those "prongs", so to speak, are gone, then DNA repair cannot repair.  One cannot be successful without the other.  There are different types of repair:direct repair (the most common), nucleotide excision repair, and methyl-directed mismatch repair.  

 

We have already discussed how cancer comes about, but what is it?  Well, cancer is a disease of multicellular organisms and is characterized by uncontrollable cell division.  This means that there is a mutation in proto-oncogenes that make them into oncogenes (These are all about dividing and dividing.) and a mutation in the tumor-supressor genes that causes a loss of function.  The changes that can cause the appearance of oncogenes are missense mutations, gene amplification, chrmosomal translocation, and retroviral insertion.  Gene amplification is when a proto-oncogene has been copied twice due to DNA polymerase basically "sliding back" while making a copy of the DNA.  Chromosomal translocation is when pieces of chromosomal DNA off of two different chromosomes merge to form a new chromosome.  Retroviral insertion is pretty self explanatory and occurs when virus DNA is inserted into the proto-oncogene.  Most cancers are caused by mutagens and a small percentage are caused by viruses.  

 

Checkpoint proteins are helpful in cancer prevention.  Cell growth is a cycle that goes from G₁ to S to G₂ to M to C and back to G₁ to start again.  To ensure the integrity of the cell's DNA before it divides, there are three checkpoints, which can be found at the ends of G₁, G₂, and M.  A cyclin/cdk complex must be made in order for a cell to pass through each of the checkpoints, however it can be stopped if the DNA is damaged.  

 

B.  Useful Materials

 

The G1 Phase Cdks Regulate the Centrosome Cycle and Mediate Oncogene-dependent Centrosome Amplification 

Centrosome amplification causes aneuploidy and is always found in human tumors.  This has caused some scientists to make the assumption that centrosome amplification has a hand in tumor biogenesis.  Centrosome amplification is caused by oncogenes and mutated tumor-supressor genes.  Aneuploidy suggests that those two things are sources of gene instability in tumor cells and generate abnormal processes in order to start and continue tumorigenesis.  In summation, oncogenes and tumor-suppressor genes use the cell cycle regulatory system to cause centrosome amplification and aneuploidy.  

 

This video really makes point mutations, insertions, and deletions easy to understand with its animations of the double helix.  Also, it mentions natural selection, a few mutagens, germ-line mutations, and has a nifty twitter advertisement to tie it all together.  Hope you like the video as much as I did.

 

Though this image doesn't mention the checkpoints in G₁, G₂, and M, the descriptions of each phase and the accompanying pictures are helpful.