Dual incision in TC-NER

Dual incision in TC-NER In transcription-coupled nucleotide excision repair (TC-NER), similar to global genome nucleotide excision repair (GG-NER), the oligonucleotide that contains the lesion is excised from the open bubble structure via dual incision of the affected DNA strand. 5' incision by the ERCC1:ERCC4 (ERCC1:XPF) endonuclease precedes 3' incision by ERCC5 (XPG) endonuclease. In order for the TC-NER pre-incision complex to assemble and the endonucleases to incise the damaged DNA strand, the RNA polymerase II (RNA Pol II) complex has to backtrack - reverse translocate from the damage site. Although the mechanistic details of this process are largely unknown in mammals, it may involve ERCC6/ERCC8-mediated chromatin remodelling/ubiquitination events, the DNA helicase activity of the TFIIH complex and TCEA1 (TFIIS)-stimulated cleavage of the 3' protruding end of nascent mRNA by RNA Pol II (Donahue et al. 1994, Lee et al. 2002, Sarker et al. 2005, Vermeulen and Fousteri 2013, Hanawalt and Spivak 2008, Staresincic et al. 2009, Epshtein et al. 2014).