Fig. 1

Models of ICL repair. a Model of ICL repair in quiescent cells (G0/G1 phase). An ICL on DNA is recognized by NER machinery. In the case of ICL-blocked transcription, two specific factors for transcription-coupled NER, CSA and CSB, are required to load the incision complex. In contrast, for ICLs in non-transcribed regions, the XPC-HHR23B complex is responsible for loading of incision complex of NER. The first incision is introduced by the incision complex composed of XPA-RPA, TFIIH, XPF-ERCC1 and XPG. After the first incision, the ICL lesion with the oligonucleotide is bypassed by a TLS polymerase such as DNA polymerase κ, DNA polymerase ζ, or REV1. The second incision is the introduced by another NER incision complex. b Model of ICL repair in S phase. ICL lesions cause stalling of DNA replication forks. The FANCM-FAAP24-MHF complex binds to a stalled replication fork and recruits both the FA core complex and the BLM-TOP3α-RMI1 complex. Activated FA core complex mono-ubiquitinates both FANCD2 and FANCI, which permits incisions of the ICL using structure-specific endonucleases such as XPF/FANCQ-ERCC1, SLX4/FANCP-SLX1, MUS81-EME1 and FAN1. The incision introduces a DSB which is repaired by. HR. Both RAD51 paralogs (RAD51B, RAD51C/FANCO, RAD51D, XRCC2 and XRCC3) and BRCA complexes (BRCA1, BRCA2/FANCD1, PALB2/FANCN, and BRIP1/FANCJ) are required for the formation of RAD51 filaments at damage sites. c Models of ICL incisions. An ICL lesion causes a stalled DNA replication fork that must be resolved by ICL incision. Three models for this process have been suggested. One model suggests that the first incision involves cleavage of the leading strand at a single stalled replication fork. The second model suggests that the first incision involves cleavage of the lagging strand at a single stalled replication fork. The third model suggests cleavage at two converged replication forks. After incision, the oligonucleotide with an ICL lesion is bypassed by a TLS polymerase, such as DNA polymerase κ, DNA polymerase ζ, or REV1, The DSB end is subsequently repaired by homologous recombination