Photolyase and cancer

Upon arriving at the beach yesterday, I lathered on the sun screen. Being relatively fair-skinned, I’ve learned my lesson in forgetting or not using enough of the stuff, and I wasn’t about to get all burned up. I don’t like eating lobster; I certainly don’t want to look like one.

But that isn’t the only reason I throw the stuff on so heavily. I’m also well aware of the tenacity and, if such a word is appropriate, vulgarity of cancer. Tanning is just a bad idea unless someone really wants to be diseased. It may look good (and not always), but I doubt that has ever brought solace to any cancer patients. Laying out in the sun without protection (as I saw a few people doing all day – it was at least 85 F, not a cloud in the sky) or jumping in one of those tanning cancer tubes is a sure-fire way to cause potentially deadly somatic cell mutations.

The way this works is that UV light slaps into the double helix structure of DNA causing an incorrect fusion in base pairs on the same side of the helix. Imagine – and apologies for the violence of it all – getting punched in the mouth. Instead of your teeth vertically matching as they do now (at least relatively), a couple teeth on the bottom row are now horizontal and facing each other. This calls for a dentist.

Different organisms have different mechanisms (dentists) for correcting damaged DNA. Naked mole rats, for example, have two genes for contact inhibition instead of the single gene virtually all other mammals have. This has resulted in no one ever recording an instance of cancer in the ugly little critters. If humans had this mechanism, cancer probably wouldn’t be nearly the problem it is.

Instead we get a number of repair mechanisms, chief among them base excision, nucleotide excision, and mismatch repair. (The mechanism in naked mole rats doesn’t repair mutated cells; it merely stops them from proliferating.) Unfortunately, the repair fidelity, just like the copying fidelity, of DNA is not perfect. Mistakes are made, mistakes are missed. We get cancer.

Part of our plight arises from something we’ve lost over evolutionary time. Most plants and other animals have a protein called photolyase which specifically seeks out UV damaged DNA.

Researchers at Ohio State University were recently able to observe exactly how photolyases perform their protective duty. The photolyase protein captures energy from visible light and uses it to project a single proton and a single electron towards a dimer in DNA. The two tiny particles then initiate a series of reactions that knock the contorted nucleotides back into place across the ladder, without needing to remove them like normal human proteins do. A proton and electron finally return to the photolyase protein, presumably so it can dash off to fix the next dimer it finds.

In other words, this dentist isn’t very gentle. He just punches your contorted teeth back into position. (Okay, it’s more elegant than that, but I had to finish the analogy.)

The article goes on to speculate as to the potential utilization of this protein in humans.

Given that photolyases were lost in evolution, it was possible that other proteins in the cell that allowed photolyases to do their job were also lost. But mice that were given the gene for the photolyase protein showed remarkable protection from UV damage. This means that in mice, the rest of the cellular infrastructure that photolyases need is still there. Chances are good that it’s there for humans as well.

There are other instances of mice being able to utilize genes not otherwise found in them, almost as if they’ve had them all along. For example, when injected with snippets of DNA for making red photo-pigment, normally dichromatic mice suddenly had trichromatic vision. This indicates an earlier evolved ability to see colors in the mammalian line that was later lost. In all likelihood, the appropriate gene(s) was probably just turned off out of a lack of need, leaving in place much of the cellular machinery needed to utilize red photo-pigment. I suspect the same is true with photolyase. If this can be extended to humans, a significant leap in the fight against many skin cancers may be on the horizon.

Advertisement

Your genes, sleep, fruit flies, mice, and Palin

Despite the fact that she is a whiny, genuinely stupid quitter, Sarah Palin has been popping up all over the place lately. Most recently she has been spouting off some garbage that Obama wants to set up a “death panel” in the health care bill. In truth, the bill calls for discussing one’s living will (and related concerns) with a doctor, should one choose to do that. This serves to better protect the interests of the patient. Such a measure could have avoided that whole Terri Schiavo fiasco. But, again, Palin is genuinely stupid. She never knows what’s going on. She makes this clear – literally – every single time she publicly speaks. She was especially clear when she said some remarkably stupid things about fruit fly research during the campaign season. I mention all this because of some recent research which relied on fruit flies*, and which can have a direct impact on the health of people.

Scientists have discovered the first gene involved in regulating the optimal length of human sleep, offering a window into a key aspect of slumber, an enigmatic phenomenon that is critical to human physical and mental health.

The article is well worth the read, and will probably give a fuller picture than I’m going to give. It’s all about a gene which has some seemingly minor variations, yet these variations (alleles) can drastically affect the health of the carrier.

The researchers found that mutated versions of the gene can affect the time some people go to bed, wake up, and how well they physically, emotionally, and mentally perform throughout the day. For instance, most people need roughly 8 hours of sleep a night, but one gene variant allows some to get back on 6 hours while not experiencing adverse consequences to their health.

And of course, this research was possible due to the contributions of various mice and fruit flies. When researchers would find a particular variant of this gene, they would ‘tinker’ with the same gene in these test subjects and measure the effects. One finding was that genetically engineered mice would compensate far less for sleep deprivation than would the control mice.

It isn’t clear yet exactly what it is about this gene (DEC2) which triggers the change in sleep need, but it may be that it makes protein transcription weaker, but other explanations are possible until more research is done.

*What genetic research doesn’t rely on fruit flies these days?