@article {32744,
	title = {Requirement of transcription-coupled nucleotide excision repair for the removal of a specific type of oxidatively induced DNA damage},
	journal = {Nucleic Acids Research},
	year = {2023},
	month = {2023/04//},
	pages = {1 - 13},
	abstract = {Accumulation of DNA damage resulting from reactive oxygen species was proposed to cause neurological and degenerative disease in patients, deficient in nucleotide excision repair (NER) or its transcription-coupled subpathway (TC-NER). Here, we assessed the requirement of TC-NER for the repair of specific types of oxidatively generated DNA modifications. We incorporated synthetic 5',8-cyclo-2'-deoxypurine nucleotides (cyclo-dA, cyclo-dG) and thymine glycol (Tg) into an EGFP reporter gene to measure transcription-blocking potentials of these modifications in human cells. Using null mutants, we further identified the relevant DNA repair components by a host cell reactivation approach. The results indicated that NTHL1-initiated base excision repair is by far the most efficient pathway for Tg. Moreover, Tg was efficiently bypassed during transcription, which effectively rules out TC-NER as an alternative repair mechanism. In a sharp contrast, both cyclopurine lesions robustly blocked transcription and were repaired by NER, wherein the specific TC-NER components CSB/ERCC6 and CSA/ERCC8 were as essential as XPA. Instead, repair of classical NER substrates, cyclobutane pyrimidine dimer and N-(deoxyguanosin-8-yl)-2-acetylaminofluorene, occurred even when TC-NER was disrupted. The strict requirement of TC-NER highlights cyclo-dA and cyclo-dG as candidate damage types, accountable for cytotoxic and degenerative responses in individuals affected by genetic defects in this pathway.},
	url = {https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkad256/7110754},
	author = {Sarmini, Leen and Meabed, Mohammed and Emmanouil, Eirini and Atsaves, George and Robeska, Elena and Karwowski, Boles{\l}aw T and Campalans, Anna and Gimisis, Thanasis and Khobta, Andriy}
}
