Genetic Mutations, Part II: Induced Mutations

It’s not just replication which is responsible for genetic mutations. Other things can happen to DNA as well. DNA does very important things, but one of the things that it isn’t good at is staying intact. DNA is not known for being a durable molecule. It is pretty fragile overall. DNA is constantly in danger of being broken or modified by a variety of physical and chemical agents.

For example, radiation is absorbed by nucleotides, which can break the molecules apart. If this happens, the bases themselves might be damaged, rendering it non-functional. Or, one or more base-pairs might be deleted. Or, they might even be added. Or both strands of the double helix might simply break, causing the entire molecule to split in two.

Many kinds of chemicals would interact with bonds in DNA and break them. For example, chemicals found in tobacco smoke are well-known to be highly reactive with DNA. So-called free radicals, which are produced normally by our own metabolism, also interact with DNA and can potentially damage it.

DNA is under constant assault. Even if replication goes well, once DNA is put together, there are many factors which are assaulting it and potentially damaging it. By one estimate, the DNA in a single human cell may be damaged a thousand times a day. A thousand times a day, something happens to your DNA. As you might imagine, there is molecular machinery that is devoted to detecting and correcting all sorts of errors that creep into DNA.

Most of these repair mechanisms share something in common. They depend on complimentary base-pairing to correct mistakes when they find them. When a mistake is detected, they cut out one or the other of the single strands of the double helix.

In spite of this molecular effort, some damage does remain unrepaired, and there can be consequences. A very high percentage of cancers are caused by genetic errors brought on by exposure to various DNA damaging agents. We call them carcinogens. Usually these cancers are caused by damage to certain classes of genes (antioncogenes or tumor suppressor genes). These genes code for proteins that are involved in regulating the way that cells normally divide and reproduce. They essentially act as ON or OFF switches for cell division. When these genes are damaged, they no longer function appropriately, and the cell begins to divide in an uncontrolled fashion. This is a common defining feature of cancers.

In my next article I will talk about the types of mutations that occur, and their specific consequences.