Repair of UV induced DNA lesions in ribosomal gene chromatin and the role of “Odd” RNA polymerases (I and III)

• The proportion of non-nucleosomal and nucleosomal rRNA genes varies during the cell cycle.
• NER is very efficient in the yeast nucleolus; non-nucleosomal rRNA genes are repaired faster than nucleosomal rRNA genes.
• RNA polymerase I-dependent TC-NER is present in yeast but not in higher eukaryotes.
• RNA polymerase I is released at UV induced photoproducts and is replaced by nucleosomes.
• After repair of UV photoproducts, RNA polymerase I elongation is needed to reestablish non-nucleosomal rRNA genes.
• Reversal of CPDs by photolyase is faster in non-nucleosomal then in nucleosomal rDNA chromatin.

In fast growing eukaryotic cells, a subset of rRNA genes are transcribed at very high rates by RNA polymerase I (RNAPI). Nuclease digestion-assays and psoralen crosslinking have shown that they are open; that is, largely devoid of nucleosomes. In the yeast Saccharomyces cerevisae, nucleotide excision repair (NER) and photolyase remove UV photoproducts faster from open rRNA genes than from closed and nucleosome-loaded inactive rRNA genes. After UV irradiation, rRNA transcription declines because RNAPI halt at UV photoproducts and are then displaced from the transcribed strand. When the DNA lesion is quickly recognized by NER, it is the sub-pathway transcription-coupled TC-NER that removes the UV photoproduct. If dislodged RNAPI are replaced by nucleosomes before NER recognizes the lesion, then it is the sub-pathway global genome GG-NER that removes the UV photoproducts from the transcribed strand. Also, GG-NER maneuvers in the non-transcribed strand of open genes and in both strands of closed rRNA genes. After repair, transcription resumes and elongating RNAPI reopen the rRNA gene. In higher eukaryotes, NER in rRNA genes is inefficient and there is no evidence for TC-NER. Moreover, TC-NER does not occur in RNA polymerase III transcribed genes of both, yeast and human fibroblast.