Xeroderma Pigmentosum with Severe Neurological Manifestations/De Sanctis–Cacchione Syndrome and a Novel XPC Mutation

Figure 1

Nucleotide excision repair (NER) pathway. Transcription coupled repair (TCR) removes DNA damage from actively transcribed genes and global genome repair (GGR) from the rest of the genome [13]. TCR starts when RNA polymerase stops at the damaged DNA, which acts as a signal for CSA and CSB binding. In GGR, the XPE protein and the XPC-HR23B complex recognize the DNA damage. Upon initial recognition of the DNA lesion, both pathways converge. The XP-B and XP-D DNA helicases unwind the region surrounding the damaged site, along with the XP-A, XP-G, and replication protein A (RPA) [14]. The XPF-ERCC1 nuclease complex and XP-G endonuclease excise the damaged DNA. The resulting gap is replaced by de novo DNA synthesis.