Welcome, Initiate, to the Central Dogma!

We’ve come a long way in a short time on Hack My Cancer — so far, we’ve explored a bit about cells and their DNA, and how DNA damage can lead to cancer. We’ve taken some detours into looking at what a gene is, and how the cellular machinery forms “pathways” that are made up of the products that genes make.

But we’ve kind of been beating around the bush about how genes are used to make these products. We’ve glossed over it in a kind of “magic happens here, then we have a protein” fashion. Time to fix that.

As we’ve noted before, DNA is big library of instructions for making the spare parts your cells need to keep functioning. It’s a library with around 20,000 “recipes” for different kinds of parts (mainly of the type we call proteins). The DNA in our cells (and that of other eukaryotes — animals, fungi and plants, basically) is stored in an envelope called the nucleus, which is like a library building with high security — anything that goes in or out must be escorted through special gates. Protecting DNA integrity is taken pretty seriously in the cell. As we saw in Cancer Biology for Patients — Episode 3, the stakes are very high — damaged DNA can mean “game over” for us.

DNA doesn’t leave this protected space (you can’t check out the original books in this library) — if a DNA “recipe” needs to be used by the cell, a temporary copy is made on a disposable type of molecule called RNA. RNA is closely related to DNA and has an almost identical structure, so it makes accurate copies of the original DNA. A really cool little molecular machine called RNA polymerase (made entirely of gene products itself!) is the “Xerox copier” that rides along a section of DNA to zip off an RNA copy (called a transcript). Other parts of the cell can send special signals (called transcription factors) into the nucleus to request copies of specific genes when their products are needed. These signals then direct the RNA polymerase to make a copy of the gene at a specific spot in all of the 3 billion letters of the DNA code.

From DNA Learning Center (www.dnalc.org)

These RNA transcripts of genes are allowed to leave the nucleus “library” — they float out into the main part of the cell, where another intricate molecular machine called the ribosome (you guessed it — also made out of other gene products itself!) reads the RNA transcripts and “translates” the DNA code on them into a sequence of chemical building blocks (called amino acids) — like miniature Legos with different shapes — that snap together to form a string, like beads. But these beads are somewhat sticky to each other, and as the string is being built, it starts to fold back on itself in very specific ways, so it forms a 3D shape instead of a straight string. Sometimes other molecular “helper” machines are needed to get the new protein into its final shape. This is how we get working, 3D “machine parts” from a long string of DNA letters! Pretty amazing. And it has to work correctly trillions of times a day in your body!

From DNA Learning Center (www.dnalc.org)

In molecular biology, we call this arrangement — “DNA to RNA to Protein” — the Central Dogma. I’m not making this up, that’s really what it’s called! So now you are initiated. No paddlings or secret handshakes are necessary.

Now here’s a little more about the DNA code that is used in genes to represent protein formulas. Remember how we said there were four DNA letters — A, C, G and T? Well, there are 20 amino acid “Legos” that are assembled in myriad configurations to make proteins. So how do we specify each of these 20 amino acids if there are only 4 DNA letters? Well, the DNA code has a dictionary of 3-letter “words” called codons. So groups of three DNA letters represent one amino acid. Now — if these letters get scrambled (by a mutation in the DNA) — the wrong amino acid can get added to the protein by the ribosome. If the whole sequence gets thrown off by a change that is not divisible by 3 letters, then everything after that point will be garbled, which can really mess up the protein made from that gene. It’s kind like if w echange dwher eth espace swer ei nthi ssentence. All the words after that point are wrong, even though all the letters are the same. This is a type of serious DNA error called frameshift.

So now you know a few more of the secrets of DNA and how it works inside the cell, through the magic of the Central Dogma of Molecular Biology!

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