Xeroderma pigmentosum group E and DDB2, a smaller subunit of damage-specific DNA binding protein: proposed classification of xeroderma pigmentosum, Cockayne syndrome, and ultraviolet-sensitive syndrome.
Xeroderma pigmentosum is a rare photosensitive syndrome that comprises eight different genetic diseases (A to G; variant (V)). Although genotype-phenotype correlations have been evaluated in most XP groups, the relationship between the E subgroup of xeroderma pigmentosum (XP-E) and damage-specific DNA binding protein (DDB) still remained a mystery. Recent studies have provided new insight for XP-E and the role(s) of DDB2, a smaller subunit of DDB. Reclassification studies have confirmed that mutations in DDB2 give rise to XP-E. The mouse model of XP-E demonstrated that DDB2 was well conserved between mouse and human and was critical in controlling proper cell-survival through regulating the tumor suppressor p53-mediated responses after ultraviolet (UV)-irradiation: i.e. defective DDB2 causes the resistance to cell-killing by UV-irradiation due to decreased p53-mediated apoptosis. These phenotypes are unique to XP-E because other XP groups show normal (XP-V) or hypersensitivity (XP-A, B, C, D, F, and G) to UV-irradiation. Thus XP-E is defined as a skin cancer prone disease with unique resistance to UV-irradiation.
Itoh
Toshiki
T
Department of Pathology, The University of Iowa, Carver College of Medicine, 200 Hawkins dr., Iowa City, IA 52242, USA. toshiki-ito@uiowa.edu
D000818:Animals; D002470:Cell Survival; D003057:Cockayne Syndrome / Q000145:classification* / Q000235:genetics / Q000473:pathology; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D010787:Photosensitivity Disorders / Q000145:classification* / Q000235:genetics / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000145:classification* / Q000175:diagnosis / Q000235:genetics
C117669:DDB2 protein, human; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53