Please also refer to our Connections to the Real World page.

DNA is hot these days, so you've probably heard a lot about it...fingerprinting, genetic blueprint, yadda, yadda, yadda. You might not know that DNA is subject to constant insults (chemically speaking) - bases fall off or get damaged or the backbone breaks, sometimes on one helix and sometimes on both. Some of this damage results from exposure to external sources, so you can do things to protect your DNA:

• Limit your exposure to the sun; use suncreen when you're outside.

• Don't smoke.

• Don't stand too close to nuclear detonations.

Unfortunately, some DNA damage is caused by internal sources that you can't really prevent. For example, the chemical nature of DNA is such that bases (the letters in the genetic code) sometimes just fall off. This is thought to occur about 10,000 times every day in every cell. Another example is that oxygen is good because we use to burn food to make energy, but a byproduct is nasty free radicals that can attack our DNA.

Fortunately, our cells have evolved efficient methods for repairing many types of DNA damage. You can appreciate how important these repair pathways are when you consider life without them. There is a rare hereditary disease called xeroderma pigmentosum (XP), which results from inherited mutations in any of several genes required to repair damage caused by exposure to UV light. Children with XP are extremely sensitive to sunlight, so that even very short exposures cause severe sunburn. Unless appropriate protective measures are taken, children with XP have a 50% chance of developing skin cancer by the time they are 8 years old. Protective measures include never going outside during the daytime (click here to read about a nighttime summer camp for kids with XP), applying sunscreen several times per day, wearing sunglasses and protective clothing, and avoiding other carcinogens that cause damage repaired by NER, such as cigarette smoke and auto exhaust.

Work in our laboratory is aimed at understanding certain types of DNA repair pathways. We are especially interested in the repair that involves recombination. DNA is a double helix, with two strands wrapped around one another. When damage is limited to one strand, as in the case of UV-induced damage, repair is relatively straightforward: the other strand still has all the information, so it can act as a template to reproduce the damaged region. When both strands are damaged, however, repair is more difficult. X-rays can cause both strands of the double helix to break. Several chemotherapy agents work by linking the two strands together so they can't be pulled apart; this is toxic to cells that rapidly dividing, which includes (but is not limited to) cancerous cells. These two types of damage are often repaired by pathways that involve recombination.

Recombination is just the mixing of DNA from different sources. You have two copies of each chromosomes, one from each parent. If one of your copies of chromosome 21 were to break, the cell can use the other copy of that chromosome to repair it. Although the two copies are 99.9% identical, there is the chance for some information on the broken copy to be replaced with information from the other copy. This is one type of recombination.

Although this discussion has focused on DNA repair, there are other times when recombination is important. One of these is during meiosis. As we just said, you got one set of chromosomes from each of your parents (that would be your father and your mother). But you can only give one set to your offspring, so when your body makes sperm or eggs, the cells need to separate out the chromosomes and give one of each pair to each egg or sperm. Turns out that process depends on recombination. Global defects in recombination during meiosis result in sterility, but restricted defects can result in a sperm or egg getting no copies of a particular chromosome or two copies. Have no copies means the embryo will have only one (from the other parent); it won't develop to term. When the sperm or egg has two copies of a chromosome, the embryo will have three; that's usually lethal, too, but can result in Down syndrome for chromosome 21. Humans aren't really so good at doing meiosis. It is estimated that 20-30% of all human conceptions fail due to chromosome imbalances. Most of these are never clinically recognized as pregnancy.

Our primary approach to addressing questions about DNA repair is through genetic manipulation of Drosophila melanogaster, commonly called the fruit fly. Drosophila is one of the premier "model organisms", which researches use to add to our basic understanding of how life works. There are several thousand Drosophila researchers just in the USA.

DNA repair pathways, like most cellular metabolic pathways, have been largely conserved through half a billion or more years of evolution. We can take a DNA repair gene from the fruit fly and identify the "homologous" gene in humans, in mice, nematodes, plants, and even in brewers' yeast (some of the other model organisms). By studying gene function in different organisms, we get a more complete understanding of the pathways through which cells repair DNA and of the functions of specific genes and proteins in these pathways.