Nucleotide Excision Repair Pathway

DNA damage occurs due to a variety of reasons: radiation, DNA-reactive chemicals in our environment and oxidative and free radical attacks. Nucleotide excision repair (NER) one of the DNA damage repair mechanisms, recognizes DNA damage based on abnormal structure and chemistry, excises and replaces them. NER consists to two types of repair: global genome NER (GG-NER) and transcription coupled NER (TC-NER).If damage is not in the actively transcribed strand of a gene, then GG-NER is initiated. A dimer consisting of XPC and HR23B appears to recognize and bind to damaged DNA. This is followed by the binding of the general transcription factor TFIIH and XPA, a DNA binding protein. Binding of XPA facilitates the binding of RPA, a heterotrimer that binds to and protects both of the separated strands in the open complex. XPG, a structure specific nuclease is then recruited followed by another structure-specific endonuclease, the XPF-ERCC1 heterodimer. Excision of damaged DNA is followed by the replicative gap-repair proteins that carry out DNA synthesis, the final nick being sealed by DNA ligase I.DNA damage detected within the transcribed strands of genes is repaired by TC-NER. CSA and CSB are necessary to recruit TFIIH to the damaged site and in helping to displace RNA polymerase and the nascent transcript so that TFIIH can access the damaged region. Following the recruitment of TFIIH, TC-NER is identical to the GG-NER pathway.