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.

Advertisements

3 comments on “Photolyase and cancer

  1. Pingback: 2010: FTSOS in review, July to September « For the Sake of Science

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s