According to Mats Ljungman, a researcher at the University of Michigan Medical School, as many as 20,000 lesions occur daily in a cell’s DNA. To repair all this continual damage, how does the cell first detect it? Ljungman’s research identified the logical candidate – RNA polymerase (the machine that reads the DNA and makes an RNA copy). Apparently, whenever the RNA polymerase encounters a lesion, it signals to p53, a master protein that activates all sorts of DNA repair processes.

According to the press release:

“These two proteins are saying, ‘Transcription has stopped,’” says Ljungman. These early triggers act like the citizen who smells smoke and sounds a fire alarm, alerting the fire department. Then p53, like a team of fire fighters, arrives and evaluates what to do. To reduce the chance of harmful mutations that may result from DNA damage, p53 may kill cells or stop them temporarily from dividing, so that there is time for DNA repair.

Recently, the ENCODE consortium determined that the majority of DNA in the human genome is transcribed:

This broad pattern of transcription challenges the long-standing view that the human genome consists of a relatively small set of discrete genes, along with a vast amount of so-called junk DNA that is not biologically active.

Of course, one could also argue that all this transcription simply speaks to the sloppy and wasteful nature of the cell. Yet here’s a thought. It would seem to me that Ljungman’s research now raises a third possibility: all that transcription is just another layer of error surveillance.

If so, what about the “two proteins” mentioned by Ljungman? One of them is the ATR kinase, a protein that consists of over 2600 amino acids. This huge protein is not only found in animals, plants, and fungi, but also in slime molds, green algae and parasitic protozoa. Removal of this protein from mice (through genetic knockouts) is lethal.

The other protein is replication protein A (RPA). RPA is actually a heterotrimeric complex built from the products of the RFA1, RFA2, and RFA3 genes (these are the gene names used in yeast). Removal of any one of these three proteins is lethal to yeast. RFA1, RfA2, and RFA3 code for proteins that are 600, 300, and 100 amino acids in length, respectively. And to make things even more interesting, RPA works hand-in-hand with Rad51, removing secondary structures from the DNA. RPA is not only found in animals, plants, and fungi, but also in green algae and parastive protozoa.

In other words, it looks eukarya have always been poised to use their RNA polymerase as an error sensing device. Whether such activity would be exploited would then probably depend on the need.