Nucleotide Excision Repair Controls RNA Polymerase II levels

CHOUDHARY, RAMVEER; MUÑOZ, JUAN CRISTÓBAL; BECKERMAN, INÉS; BOUVIER, LEÓN ALBERTO; FOIANI, MARCO; MUÑOZ, MANUEL JAVIER

Ottawa

Conferencia; 13th International Conference on Environmental Mutagens; 2022

Environmental Mutagenesis and Genomics Society

DNA is the only biopolymer that is neither disposable nor recyclable so it must be repaired when damaged. Among the various repair systems that human cells have, the nucleotide excision repair (NER) system is the most relevant for repair of UV-light induced lesions. Damage detection by NER system occurs by two different DNA-sensing mechanisms that then converge on the same machinery that repairs the damage: transcription-coupled repair (TCR) and global genome repair (GGR). At the same time, it is well known that UV-induced DNA lesions favour the degradation of RNA Polymerase II (RNAPII). The lysine residue responsible for RNAPII major subunit ubiquitination and degradation was recently identifies, showing an unanticipated relevance for RNAPII levels in the control of gene expression and cell survival upon UV-induced DNA damage. However, the mechanisms that lead to the degradation of RNAPII have not yet been elucidated. One hypothesis, known as the last resort theory, states that RNAPII degradation is dependent on TCR. According to this theory, the arrest of RNAPII in DNA - given its inability to transcribe the lesions - would lead to its degradation, thus allowing access to the repair machinery. Here, we propose that RNAPII levels determine cell viability and are mainly controlles by an unexplored GG-NER-dependent mechanism, in which RNAPII can be degraded in trans.