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MAW Cancer Chronicles #10:
CANCER IN A NUTSHELL - PART TWO
STRUCTURE AND FUNCTIONS OF DNA,
THE MAIN TARGET OF CANCER CHEMOTHERAPY



25 years ago, at about this time of year, while anxious over finishing my Ph.D, I found out that I had cancer and it would take three weeks for the specialists at Dana Farber to see me. While I had time on my hands I learned about cancer. While we are waiting for the time that I will describe the staging and treatment of my cancer, allow me to give a description of cancer and its treatment in a greatly over-simplified form. I hope you find it informative, and will help you to understand how chemotherapy works as I describe it later.


CANCER IN A NUTSHELL - PART TWO STRUCTURE AND FUNCTIONS OF DNA THE MAIN TARGET OF CANCER CHEMOTHERAPY


DNA is marvelously engineered molecule which contains the information that allows life to function and reproduce itself. There are whole courses that are devoted to DNA, and numerous libraries have been written about it. I am summarizing the info equivalent to a 1500+ page molecular biology book, so I will have to leave some things out. I will focus on aspects that are important to cancer and chemotherapy targets. I see these as three broad categories: the structure of DNA, the functions of DNA, and the role of DNA in the cell cycle. This is the most technical I will get, I am sorry but if anti-cancer drugs attack DNA, understanding a bit about its structure and functions are necessary for understanding chemotherapy. We will return to the narrative soon.


STRUCTURE OF DNA
DNA stands for deoxyribonucleic acid. No doubt you have seen a structure of DNA which looks like a twisted ladder, the famous double helix. This sides of the ladder are the same throughout of the length of the molecule. Consisting of a chain of a sugar (deoxyribose) connected with phosphates (derived from phosphoric acid) to form both sides of the ladder. The steps of the ladder are four molecules (nucleobases) that are represented by letters A, G, C, and T. The exact order of these bases is the code of life. The reproducibility of DNA is guaranteed because a step is a pair of bases weakly connected either as A-T or G-C or the reverses. To summarize, DNA is a like two chains with identical links (sides of the ladder). Each of the links has attached to it one of four bases (A, T, G, or C) which connect to an adjacent chain to form the steps of the ladder. The nucleobases are flat disc like molecules, and the DNA is tightly packed so that each disc is stacked on top of the one below it. This means that in the ladder analogy the steps of the ladder lie on top of each other with no space between steps.


FUNCTIONS OF DNA
DNA has three main functions:
1) Storage of genetic information - Sections of DNA called genes store the code which determines how to make a protein. Genome is the entire set of the genes and non-gene DNA for an living thing. Genes are coiled up in the chromosomes that are stored in the nucleus of the cell. Proteins are the most versatile of biomolecules and they perform many functions including catalyzing reactions, transporting molecules such as oxygen, controlling biological processes, and providing structural integrity.


2) Reading of the genes - Special proteins split open a piece of the DNA chain in half and read one side of the DNA and make a copy of the gene as another nucleic acid called RNA (riobonucleic acid, like DNA with a different sugar). This process is called transcription (think transcribing a document) . The code is read as three letter "words" called codons. There are 4 bases, so the first letter in the word has 4 possibilities, the second letter four, and the third letter four also. That means there are 4 x 4 x 4 = 64 possible words. Each word represents amino acid. There are also words for "start" at the beginning of the gene and "stop" at the end of the gene. Amino acids are strung together in the proper order from the code from the gene in protein factories called ribosomes.


3) Replication - The pairing of A-T and G-C ensures that the two sides of the DNA molecule are complimentary. The DNA is split into two strands and proteins find free floating complementary bases and attach these to the single strands to reform double strands of DNA that are an exact copy of the original DNA. Double strand DNA --> Two single stands that are complementary ---> Addition of bases, sugars, and phosphates --> Two exact copies of the original DNA.


SUMMARY
1) DNA is a tightly packed double helix like a ladder with genetic information stored in the steps of the ladder.
2) The steps of the ladder are molecules abbreviated A,T,G,C that pair up in DNA as A-T and G-C.
3) The DNA stores the genetic code in a specific order in the two complementary strands.
4) Proteins read a gene on DNA and store the info in RNA.
5) RNA takes the the genetic information to ribosomes to make proteins.
6) DNA can be split into two strands that new A,T, G, and C molecules are added to produce two copies of the original DNA


Next up the cell cycle


Stay tuned for more of the story.


(Cancer Chronicles is a series of status updates that account the events of 25 years ago when I went through a bout with cancer. Its purposes are multi-fold: catharsis, education, information, celebration, etc. )


This originally was posted to facebook October 4, 2012.

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