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1) find out what is causing the problem
2) figure out the solution to the problem
3) figure out how to get the solution To the problem
4) solve the problem.

Certain cell cycle quality control checkpoints are in place that make sure that the cell does not advance to the next stage in the growth cycle until quality control checkpoints have finished. The cell will be instructed to wait until DNA repairs are made, if repair is possible, otherwise apoptosis (programmed cell suicide) will be invoked.


cycle arm rotates as a gif animation	show_correlated_mitosis_animation_here	programmed cell death animates here

-- after Alberts et. al. p 868

Promotion
We all have cells in our body that are "promoted", that is, one or more of their quality control checkpoints don't work. In most cases there multiple quality control checkpoints, nothing bad happens until all the checkpoints are broken.

These checkpoints are called "tumor suppressors" since historically it has been noted that, when they are broken or missing, tumors appear. One might prefer to think of them as quality control (QC) agents. These QC agents have names. Before we can discuss their names we need to take a quick biology 101 aside, you read, you graduate, begin.

In the nucleus of each cell two sets of 23 "autosomes" and 1 "sex" chromosomes appear. These two sets, one from mom, one from dad, contain most of the cell's DNA. Think of each chromosome as an instruction book on how to make some aspect of a human being. Twenty three of the books are rated "G". A twenty fourth book is rated either "X" or "y". If the book is rated "X" it holds twice the information. If the book is rated "y", it holds about half as much since the y is really a shriveled tiny excuse for a chromosome.

Each chromosome consists of a sequence of roughly 3 billion/24 nucleotide bases that come in four flavors. Four is a nice number. Four nucleotide bases (C, T, A, and G) of DNA are transcribed into four nucleotide bases of RNA (C, U, A, and G). Triplets of RNA, for example, "GAG" are then translated into proteins. The "GAG" codon codes for Glutamate, 1 of 20 amino acids that your mother wanted you to get when you ate your dinner. Long strings of amino acids are called proteins and come in two kinds, globular and fibrous. Globular proteins include complex enzymes, incredible micromachines that facilitate the chemical reactions of metabolism. These globular proteins must be carefully folded to do their job, which usually consists of making a little hairball nest for one or two chemical reactions of metabolism. Fibrous proteins like collagen, keratin and actin make skin, hair and muscle. Where else would they put our enzymes?

The cell's nuclear DNA, 23 + 1 sexX chromosomes courtesy of mom, plus 23 + 1 sexY chromosomes courtesy of dad, contain the blueprint for ALMOST everything. Almost means that the compartments of a cell, called organelles, are not created from a DNA blueprint, but are instead duplicated from existing copies when the cell divides. Another "almost" are the mitochondria, the "batteries" of the cell that have their own little piece of DNA. Mitochondrial DNA comes only from mom and inside each mitochondrion is some graffiti that says, "Eve was here".

The instructions for expression and regulation of all body processes (except the two "almosts" mentioned above) are contained in the DNA. Each atomic instruction is called a gene. To a first approximation, every gene contains the instructions that will code for a single protein. Sometimes genes occur in groups called operons. Regulatory machinery called promotors and repressors are encoded right onto the DNA, usually upstream of the gene. Promotors are little sections of DNA code, that tell a locomotive sized enzyme named DNA polymerase to switch onto the track and express the instructions for a given protein. Repressors are little sections of DNA that code for proteins that throw themselves onto the DNA railroad tracks which makes the conductor have to stop the train and go look for other work. Repressors can be located anywhere. And since I have strayed so far, I may as well tell you about transposons, which are little DNA hobos that appear to have no other purpose than to get up and plant themselves in other sections of our DNA at random. These dangerous little creatures lurk everywhere and are moved around nefariously by the evil black locomotive called "transposase", who, given time, will kill us all, and as if that wasn't enought, will produce those horrid age spots.

Due to the migration of transposons (hobo DNA), external environmental influences (irradiation or exposure to carcinogens), these checkpoints get broken.
When all the quality control checkpoints in a single cell are broken cancer is ready to happen.
There are about 100 trillion cells in the body. Most contain 2 meters of tightly compacted DNA. 200 trillion meters of DNA is a long instruction tape, with lots of opportunity for mistakes. Several simultaneous mistakes in close quarters are required to cause cancer.

Our quick biology 101 aside is done, congratulations, you have graduated. Now for the names of the quality control checkpoints. Located on chromosome 17, a small but important chromosome is our hero, a master control gene called p53. Sometimes heroes get killed off by bad guys like transposons, or make a bad decision like the president, which is sad. When p53 is doing his normal hero job, he is a master regulator in charge of three other genes, p15, p21 and p27. These genes code for special proteins that do the quality control checkpointing in the cell cycle, that make for a prosperous nation and healthy economy. The genes (remember genes live on chromosomes) p15, p21 and p27 code for enzymes called "kinases". And for right now, kinases are really the center of our story. Remember the part about kinases, someday it might save your life...

Role of Hormones
Hormones are chemical messengers that tell cells to change. They are small molecules. The difference between a normal cell and a cancer cell is not the hormone signals they receive, but rather What They Do In Response to the Hormone Signal. Remember that cancer cells are like spoiled children. They listen to signals they shouldn't listen to, and do unpredictible things when they do.

Back to kinases. Kinases do something interesting, 24 hours a day, 365 days a year, including Sundays and holidays. They put phosphates on. Phosphates are those things that Rachel Carson didn't want you washing your clothes in.

Kinases are important in signalling and trafficking. We will get back to them. We need to mention three other players, when we understand how all these interact then we will be done.
1) Glycosylation
2) SNARES
3) Metalloproteases

Cells are studded with a forest of little trees called receptors. There are receptors for every imaginable thing on the surface of a cell. Each receptor has a little signature on top of it, which are like colored flags tied in the top of the branches. These colored flags can be in a line, they can be strung along the branches, and they have their own unique pattern. Every sickness has its own little pattern flags and that pattern is what our immune system uses to make us better.
The different colored flags are sugars. Sugars like glucose, mannose, galactose and even one that is just as simple as the first three, but with a big bad wolf name, N-Acetylglucosamine, or gluNac for short.

Inside the cells, there is stellated network of rails that connects various parts together. This internal network of actin protein fibers has cellular compartments running along it 24 hours a day, powered by tiny molecular motors of kinesin. When a compartment arrives at its destination, it has to have a docking port in order to fuse and unload its cargo. Little proteins on the compartment and destination called snares, wave their arms at each other, hoping to make the docking work.

Remodeling.
Have you ever torn a wall out to do some remodeling?
Have you ever been sitting in your living room while someone tears the wall out without telling you first, as in EARTHQUAKE?

That is what metalloproteases do. They are enzymes whose job it is to tear out the walls of cells to rebuild, remodel, and also engulf and devour.

Somehow, and my job is to find out exactly how, somebody fills a work order out.
This work order resembles the old college prank of having pizza delivered to a vacant lot. Only this prank is a trifle more fiendish, and the lot isn't vacant.

When cancer fills out work orders for all the cells around it, it signals them, via metalloproteases, to tear the walls out, of all the houses in the neighborhood so it can go steal the color TV's, VCR's and bedroom suites and make one big happy pawn shop of parts that can be used to invade more neighborhoods.

1) evil transposon lands on quality control checkpoint.
2) cell grows without quality control and makes chromosomal mistakes called translocations.
3) cell goes primal and says, "Hey, Me Cave Man" and starts growing fast, furiously and without listening to its neighbors, reading the local building ordinance or even filing a building permit.
4) cell tells neighbors, "wrecking ball come now" and the helpless villagers all stand helpless while MetalloMan moves into town.