Despite some ear ly uncer ta in ty, the presentv iew is thatXPE patien ts and cells lack the p. The ro le of th is pro te in isstillunc lear butitis invo lved in repa ir of non transcr ibed reg ionsof DNA andits exp ress ion is dependenton p. These patien ts generally havemi ld symp toms and the mu tations in XPF result in dec reased leve lsof the endonuc lease activity and a result ingslow exc is ion of pho toproduc ts. XPG encodes an endonuclease that cleaves on the side of an UV photoproduct, and which is also a cofactor that increases the activity of aglycosy lase. Many of these severe XPG cases had mutations that truncate the XPG protein, but in one case a mild phenotype occurred in a patient who had a missense amino acid <a href="http://www.targetmol.com/compound/Diclofenac">Targetmol's
Diclofenac</a> change in one allele and higher NER in having high risk for skin cancer but rare to no neurological abnormalities.Consistent with the symptoms of XP patients, mice that lack XPA or XPC show increased UVB carcinogenesis. CS patients are sun sensitive but do not develop cancers, setting this disease apart from XP.In addition to patients who show combined XP and XPCS symptoms there are a set of patients who only have CS.These correspond to mutations in one of two genes, CSA and CSB, group A being the more common. Three patients from families are known from XP complementation group B which also show CS symptoms. The CS gene products are involved in coupling excision repair to transcription, but their precise function is not yet clear.They may be involved in the ubiquitination and degradation of stalled RNA pol II at damaged sites.Cockayne syndrome and XP group C make an interesting contrast.CS cells repair only transcriptionally inactive genes, whereas XP group C cells repair only transcriptionally active genes.They show a similar increase in sensitivity to cell killing, indicating that all regions of the genome must be repaired for normal survival.But only XP group C shows elevated mutagenesis and carcinogenesis.This comparison indicates that defective repair of transcriptionally inactive genes is more important for carcinogenesis in human cells and tissues.The hair has characteristic tigertail banding visible under polarized light.The patients often have an unusual facial appearance, with protruding ears and a receding chin.Mental abilities range from low normal to severe retardation. Several categories of the disease can be recognized on the basis of cellular responses to UV damage and the affected gene.Severe cases have low NER and mutations in XPB or D as described above.A third category involves another unidentified gene called TTDA and lacks major UV sensitivity, and appears to have an unstable TFIIH. Polymorphisms in several DNA repair enzymes have been reported in populations with increased susceptibility to malignacy. The face, head, neck, backs of the hands and forearms are the predominant sites.Additionally, skin cancer incidence increases with age, suggesting that cumulative exposure is responsible for the development of these cancers. Clinically the lesions present as an erythematous, indurated papule, plaque or nodule with adherent scale.