Multiple roles of ubiquitination in the control of nucleotide excision repair

Nucleotide excision repair (NER) is a remarkably versatile DNA repair system, essential for maintenance of genomic stability. Hereditary alterations in NER enzymes can result in increased cancer propensity, but also in developmental, neurodegenerative, and progeroid syndromes. NER can be operationally divided in three subtypes, which share many common steps: global genomic repair (GGR) operates on the whole genome level, transcription domain-associated repair (DAR) is a concentration of NER activity within transcription factories, and transcription-coupled repair (TCR) provides faster repair of the transcribed strand of active genes. Interestingly, ubiquitination plays an important role in all three classes of NER, as well as in associated phenomena, such as damage signalling by histone ubiquitination, and degradation of stalled RNA polymerase II when repair does not occur in a timely manner.

► Nucleotide excision repair (NER) is one of the most important DNA repair systems.
► It consists in three sub-systems: GGR, TCR and DAR.
► Ubiquitination plays important regulatory roles in all three sub-systems of NER.
► Ubiquitination also operates in damage signalling and RNA polymerase II degradation.