4. Conclusions
DNA damage can occur throughout life; therefore, it is fundamental for DNA repair to occur to preserve the genetic material encoded. NER is one of the repair pathways, and it is responsible for the removal and repair of bulky lesions within the DNA. NER has two subpathways, GG-NER and TC-NER, both of which play an important role and require the recruitment and activity of the TFIIH complex. TFIIH is important for damage verification, unwinding of the DNA, and holding open the excision bubble for the other NER proteins to function. When defects occur in the proteins in TFIIH and the proteins throughout the rest of the pathway, genetic disorders will occur with varying clinical phenotypes and severity. Proteins within the TFIIH complex also provide therapeutic targets in cancer chemotherapeutic treatments to different cancers and understanding mechanisms of resistance within them as well.
However, despite the extensive research and knowledge on the NER pathway and the TFIIH complex, there are still many knowledge gaps regarding the detailed functions of TFIIH in NER. For example, how do XPB and XPD coordinate to open the two DNA strands? What exact roles does TFIIH play in TC-NER? Why germline mutations in XPD, some of them occur in residues close to each other (e.g., Arg601 and Gly602)(Lehmann, 2001), exhibit significantly different clinical phenotypes? More research is needed to further elucidate the mechanisms and the role of each of the individual subunits of the TFIIH complex in both transcription and the NER pathway.