5. Which proteins DIFFER between the global genome repair (GGR) and transcription-coupled repair (TCR) pathways? Briefly describe the presumed role of each of these different proteins (in GGR or TCR). Do NOT describe the roles of proteins used in common by GGR and TCR. (5 points)
The protein specific for GGR is XPC. When I first made up this question, I was under the impression that hHR23B is also specific for GGR. On reviewing my lecture notes just now, however, I found no indication that hHR23B is not also involved in TCR. When I used PubMed to search the recent literature for experimental evidence one way or the other, I found some evidence that hHR23B also plays a role in TCR (Biochem Biophys Res Commun 2000 268:210-5), so in grading this answer I gave full credit for either answer: "XPC" or "XPC + hHR23B". The proteins specific for TCR are RNA polymerase II, CSA and CSB.
GGR is initiated when XPC and hHR23B bind to a damaged site, partially unwind the DNA at that site, and attract the other NER proteins (XPA, TFIIH, RPA, etc.) to the site. In contrast, TCR is initiated when RNA polymerase II stalls at a damaged site in the template strand. Under these conditions, CSA and CSB, which are bound to the RNA polymerase, assist in recruiting the other NER proteins (XPA, TFIIH, RPA, etc.) and in displacing the RNA polymerase so that the NER proteins can gain access to the damaged site. In the case of TCR, the initial unwinding is probably accomplished by RNA polymerase and other enzymes of the transcription complex, since template unwinding is essential for transcription.
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