RNA Polymerase II and
Nucleotide Excision Repair Pathway
It has been shown that RNA Polymerase II, when confronted with a lesion, will stall. When it stalls, it sends a signal to the rest of the cell indicating that the DNA needs to be repaired. So far, scientists have found out a number of things that occur during this process. These include: the ubiquitination and hyperphosphorylation of RNA Polymerase II, the recruitment of TCR-specific proteins including CSA and CSB, and the movement of RNA Polymerase II from the site of the lesion (Bregman et al. 1996). The ubiquitination, in this case, does not target the RNA Polymerase II for direct degradation. It could, however, alter its confirmation, allowing it to help excise the lesion. Conformation flexibility has been reported before; using RNA Polymerase that has not been ubiquitinated, but the same concepts could be used in this case as well. There have been three categories of high-variance regions, including: cleft, cavities and interfaces, and unstructured or highly flexible regions. These regions aid in the protein to properly bind to the DNA, bind the nucleotide triphosphates, and bind to the other proteins that are intimately involved in the transcription process (Kostek et al. 2006).
In addition to the RNA Polymerase II stalling, there are other factors that are critical in properly repairing the lesion. These factors include many of the RAD proteins, the CSA and CSB proteins as mentioned before, and especially TFIIH. Each of these factors are recruited one by one to the lesion site, and each one is dependent on binding to TFIIH using CSA as a scaffolding protein (Guzder et al. 1996, Bardwell et al. 1994, Henning et al. 1995). Even with all this information on how the TCR pathway may work, a lot is still unknown. With Kornberg’s contributions to the molecular structure and mechanism of RNA Polymerase II, it is just the starting point to figuring out a mountain of other information, including the molecular mechanism of TCR. This new information could hopefully one day find better treatment options for individuals suffering from Cockayne Syndrome and other diseases associated with a defective TCR pathway.