Molecular Machines Are Amazing Alone, but When They Cooperate -- Wow!
News from New York University School of Medicine, reported in Nature, is fragrant with the smell of intelligent design. Without, of course, mentioning it by name. The researchers describe a cooperative, machine-driven DNA repair system. From the press release:
Our health depends in large part upon the ability of specialized enzymes to find and repair the constant barrage of DNA damage brought on by ultraviolet light radiation and other sources. In a new study NYU School of Medicine researchers reveal how an enzyme called RNA polymerase patrols the genome for DNA damage and helps recruit partners to repair it. The result: fewer mutations and consequently less cancer and other kinds of disease. (Emphasis added.)
The article not only describes how several interesting molecular machines cooperate in the task, but resolves a mystery about an activity that previously was thought wasteful or useless. No word, in case you wondered, about evolution. Even the paper in Nature only mentions "evolution" twice to say that the multi-part operation is "conserved" or "preserved" from bacteria to humans -- in other words, no evolution has occurred.
RNA polymerase -- the machine that translates DNA into RNA -- is the star player. It patrols the DNA like an automated inspector on train tracks. When it encounters a break, it stops and waits. The problem is, when it stops, it stalls over the break, preventing repair machines from reaching it. Not to worry. Everything is under control.
In the new study, the NYU School of Medicine researchers reveal how another enzyme called UvrD helicase acts like a train engine to pull the RNA polymerase backwards and expose the broken DNA so a repair crew can get to work....
The study by Dr. Nudler's group and colleagues in Russia used a battery of biochemical and genetic experiments to directly link UvrD to RNA polymerase and to demonstrate that UvrD's pulling activity is essential for DNA repair. The lab results also suggest that UvrD relies on a second factor, called NusA, to help it pull RNA polymerase backwards. Those two partners then recruit a repair crew of other proteins to patch up the exposed DNA tracks before the train-like polymerase continues on its way.
Each of these machines is powered by ATP and built by the same DNA that it repairs! One can't help but recall Dean Kenyon's reaction in Unlocking the Mystery of Life to this kind of discovery: "This is absolutely mind-boggling to perceive, at this scale of size, such a finely-tuned apparatus, a device that bears the mark of intelligent design and manufacture." Each of these machines is complex enough in itself. To see them working as a cooperative team is all the more wonderful.
More on how a mystery was solved by the researchers at NYU:
According to Dr. Nudler, his team's study offers a convincing justification for a puzzling phenomenon known as pervasive transcription, which he calls "one of the most enigmatic and debated subjects of molecular biology." The question, he says, boils down to this: Why do RNA polymerases transcribe most of the genome within humans and other organisms, converting vast stretches of DNA to RNA, when only a tiny fraction of those resulting RNA transcripts will ever prove useful? Isn't that RNA polymerase activity a waste of energy and resources?
"Our results imply that a major role of RNA polymerase is to patrol the genome for DNA damage," he says. "This is the only molecular machine that is capable of continuously scanning the chromosomes for virtually any deviation from the canonical four bases in the template strand: A, T, G and C." The polymerase's extensive transcription activity, then, might be well worth the effort if its continuous vigilance also ensures that any DNA damage gets fixed through the assistance of the pulling factors and other collaborators.
So it wasn't wasteful after all. And we know from the ENCODE project that most (if not all) of the non-protein-coding DNA is important for regulation and other functions. This amplifies the importance of RNA polymerase's constant "vigilance" in inspecting the entire genome.
Included in the article are descriptions of bad consequences when RNA polymerase, UvrD helicase and the other machines don't work properly (perhaps due to mutations in their genes). Hair can turn brittle; children may age prematurely; others may suffer from exposure to sunlight. Those are the lucky ones who don't die without this vital repair mechanism.
The study reveals a "major new role of RNA polymerase and other enzymes in DNA repair." Notably, it's not the only repair system. Our genomes are protected by multiple levels of monitoring and repair, so that most of us carry on from day to day, completely oblivious of the multiple information-guided processes in our cells that make life work. There are systems that can fix double-stranded breaks. There are systems that can replace incorrect DNA bases (letters) in the code. There are even machines that can push the panic button when errors are catastrophic, causing a damaged cell to shut down.
For science to comprehend these systems, it needs a framework fit for the information age. It needs familiarity with robotics and multi-level control. The biology of Charles Darwin's antiquated Victorian world, which imagined systems emerging from unguided processes, is hopelessly inadequate. Darwin did not foresee, and could not have fathomed, the technology at the basis of life.
Image source: Arizona Corporation Commission.