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When a segment of the template strand of DNA is damaged due to factors such as UV radiation, a lesion is created that would effectively block the passage of RNA polymerase II during transcription.

When such stalling occurs, a mammalian cell would usually deploy various transcription-coupled repair factor, such as the XP group of proteins to give provide a proper basis of the lesion and to orient other enzymes in. The endonuclease would cut out the damaged bases, and the DNA polymerase and DNA ligase would, respectively, add the new bases and correctly anchor them onto the template strand.

I fully realize that during the process in which the RNA polymerase II was stalled to the arrival of the transcription-coupled repair factors, some sort of cell signaling must have occurred. However, I could not find any sources that would tell me the specificity of such phenomenon. Therefore, I hope this forum could explain such matter.

Thank you very much!

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The beauty of RNA polymerase II is its faculty to act like a sensor towards damage to genetic data. The response of the RNA molecule is variable on the type of DNA lesion which presents itself. DNA lesions may be a consequence of ultraviolet radiation, or through the metabolic by-products of oxidative free radicals. These specific faults within the lesion, it is hypothesised, are respectively detected by the RNA pol II molecule by interaction with its active site.

Various endogenous modifications made to the DNA strand Some examples of different genetic damage to bases

In the example you provided, namely, RNA is limited fully or partially from transcription elongation, this is detected as an inhibition of the active site. This could be caused by presence of cyclobutane which distorts the shape of the DNA molecule such that it prevents further RNA synthesis.

Therefore, in the incident that RNA pol II is fully stalled, the first co-factor to commence the signalling process is Transcription factor II H, which repositions the polymerase molecule away from the site of damage. Although it is not fully known, this allows the XPG, having certain endonuclease properties to excise the faulty bases (thymine dimer, for instance).

In order to fully repair the molecule, DNA polymerase uses translocation to reinsert the correct complementary bases. PCNA, proliferated cell nuclear antigen, may be used as a DNA clamp to increase the processivity, ability for multiples catalyses without leaving the substrate, of DNA polymerase. Then protein complexes XPD operates as a ligase.

Therefore TC-NER, transcription-coupled repair, is believed to begin at a blockage of the active site of RNA pol II!

Best regards More information regarding this hypothesis and function may be found from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4984683/ and https://www.ncbi.nlm.nih.gov/pubmed/11245433

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