The factors XPB and XPD are Targetmol’s Pregnenolone helicases of the multisubunit transcription factor TFIIH that open w basepairs of DNA around the damage.XPA probes for abnormal backbone structure, conrming the presence of damage.If damage is absent, NER can be aborted at this stage.Stabilization of the opened DNA is achieved by the singlestranded binding protein RPA by binding to the undamaged strand.Endonucleases XPG and ERCCXPF, respectively, cleave the and borders of the opened stretch of DNA of the damaged strand, releasing a basepair oligonucleotide containing the lesion.Replication factors DNA polymerase is required for repair synthesis and regulates repair patch size by association and dissociation from DNA polymerases. In the absence of PCNA, repair events are frozen, leaving DNA stabilized in an incised state.More than proteins participate in NER, and in vivo evidence suggests that individual components are assembled at the site of the lesion in a stepwise process.Following a single repair event, the entire NER machinery is disassembled again.Although DNA repair efciently disposes of most DNA damage, a substantial number of lesions escape repair, interfering with replication and transcription.To minimize cell death resulting from replication blockade, a process known as translesion bypass synthesis has evolved, allowing replication to proceed past the damage. Replicative DNA polymerases synthesize DNA with a high degree of accuracy, but are blocked by helixdistorting lesions.In contrast, TLS DNA polymerases are able to synthesize DNA past lesions, but with lower delity than replicative polymerases, introducing mutations. Rather, damage recognition in bacteria is strongly dependent on the size and the structure of the aromatic rings of the adduct.The importance of formamidopyrimidine DNA glycosylase in the repair of AFBFAPY remains controversial.Homologues for most of the proteins involved in yeast NER have been identied in humans.The RADRAD complex, for which there is no mammalian homologue, is required for yeast GGR, but not for TCR.The properties of RADRAD suggest that it plays a crucial role in the initial damage recognition of lesions in nontranscribed regions of the genome. Mutations in yeast NER genes compromise repair activity as they do in the corresponding humans genes, with the exception of rad. RAD is essential for both TCR and GGR in yeast, whereas XPC is required for GGR, but not TCR in humans.It is thought that replication forks collapse when encountering AFB DNA adducts, leaving single strands that are likely to be repaired by homologuous recombination.Furthermore, it has been suggested that in the absence of NER and recombinational repair, mutagenesis in yeast ensues via the errorprone TLS pathway. Surprisingly, loss of AP endonuclease, which is involved in the repair of apurinic sites, reduced the mutagenic effects of AFB.It was expected that loss of AP endonuclease would lead to an accumulation of AP sites, increasing mutation frequency.The dependence of repair efciency on adduct structure in mammalian systems is not unique to AFB.DNA adducts induced by the polycyclic aromatic hydrocarbons are also primarily repaired by NER.Interestingly, a recent study in human cells has shown that, while structural differences in adducts induced by dibenzo pyrene are reected in differential repair rates, structurally diverse adducts induced by benzo.