Xeroderma pigmentosum A

Yarosh, D., et al.. Effect of topically apphed T4 endonuclease V in liposomes on skin cancer in xeroderma pigmentosum a randomised smdy. Lancet, 357, 926-29, 2001. 

Exposure to UV radiation from sunlight is the major cause of human skin cancer. Skin tumors from patients with Xeroderma pigmentosum, a DNA-repair deficiency associated with increased sensitivity to UV, show a particularly high frequency of these CC to TT transitions (Dumaz et al., 1993). Mutations at dipyrimidines have been observed in the normal skin of sun-exposed skin cancer patients (Jonason et al., 1996 Nakazawa et al., 1994 Ren et al., 1996a). The localization of mutations in skin shows striking differences with other types of cancers, with hotspots at codons 177-179 and... 

Nucleotide Excision Repair Was Elucidated Through Study of Xeroderma Pigmentosum, a Hereditary Predisposition to Skin Cancers... 

XPA-MBD (minimal DNA-binding domain of xeroderma pigmentosum A) ZnS4 327.6 4.9 0.84 CP/QCPMG [48]... 

The very first direct observation of a Zn in a metalloprotein was reported in 2001 [48]. Using Zn-enriched sample, Zn static spectrum of the minimal DNA-binding domain of xeroderma pigmentosum A (XPA-MBD), a 14.7 kDa protein, was observed at 25 K by CP/QCPMG method at 9.4 T. The local Zn environment was found to be similar to that of Zn[SC (NH2)2]4(N03)2, a model compound, su esting a sulphur coordination. 

J. E. Cleaver, Xeroderma pigmentosum A human disease in which an initial stage of DNA repair is defective, Proc. Natl. Acad. Sci. U.S.A. 63, 428-435 (1969). 

Currently, 13-cis-retinoic acid is the most studied chemopreventive agent that decreases the incidence of second primary tumors in patients with head-and-neck cancer, reverses premalignant lesions, and reduces appearance of nonmelanoma skin cancer in patients with xeroderma pigmentosum. Unfortunately, this vitamin A derivative has a significant clinical toxicity, which limits its utility in a practice setting. 

P., Hubert, M., Decroix, Y. and Sarasin, A. (1986). Deficiency in the catalase activity of Xeroderma pigmentosum cells and simian virus 40 transformed human cell extracts. Cancer Res. 46, 538-544. 

Theron T, Fousteri MI, Volker M, Harries LW, Botta E, Stefanini M, Fujimoto M, Andressoo JO, Mitchell J, Jaspers NG, McDaniel LD, Mullenders LH, Lehmann AR (2005) Transcription-associated breaks in xeroderma pigmentosum group D cells from patients with combined features of xeroderma pigmentosum and Cockayne syndrome. Mol Cell Biol 25(18) 8368-8378 Thiriet C, Hayes JJ (2005) Chromatin in need of a fix phosphorylation of H2AX connects chromatin to DNA repair. Mol Cell 18(6) 617-622... 

The deficiency of an excision endonuclease may produce an exquisite sensitivity to ultraviolet radiation in Xeroderma pigmentosum. Which of the following functions would be absent in a patient deficient in this endonuclease ... 

Investigations by Yarosh over almost two decades have proven that liposomal carriers allow uptake of a DNA repair enzyme into the skin [57], This uptake significantly reduces the number of new actinic keratoses and new lesions of basal cell carcinoma in patients with xeroderma pigmentosum who were treated for 12 months [58], Moreover, in a mice model, transdermal vaccination by antigen incorporation into liposomes has also been demonstrated [59,60],... 

Natarajan, A.T., Verdegaal-lmmerzeel, E.A.M., Ashwood-Smifh, M.J. and Poulton, G.A. (1981) Chromosomal damage induced hy furocoumarins and UVA in hamster and human cells including cells from patients with ataxia telangiectasia and xeroderma pigmentosum. Mutation Research, 84, 113-124. 

Xeroderma pigmentosum is caused by a defect in excision repair of thymine dimers, most freguently due to the absence of a UV-specific excinuclease, an enzyme that helps remove thymine dimers. 

Park DJ, Stoehlmacher J, Zhang W et al. A Xeroderma pigmentosum group D gene polymorphism predicts clinical outcome to platinum-based chemotherapy in patients with advanced colorectal cancer. Cancer Res 2001 61 8654-8658. 

Maher, V., Rowan, L.A., Silinskas, K., Kateley, S., and McCormick, J. (1982). Frequency of UV-induced neoplastic transformation of diploid human fibroblasts is higher in xeroderma pigmentosum cells than in normal cells, Proc. Natl. Acad Sd. 79,2613. 

Peak, J.G, Pilas, B., Dudek, E.J. Peak, M.J. (1991) DNA breaks caused by monochromatic 365 nm ultraviolet-A radiation or hydrogen peroxide and their repair in human epithelioid and xeroderma pigmentosum cells. Photochem. Photobiol., 54, 197-203... 

When Pol II transcription halts at the site of a DNA lesion, TFIIH can interact with the lesion and recruit the entire nucleotide-excision repair complex. Genetic loss of certain TFIIH subunits can produce human diseases. Some examples are xeroderma pigmentosum (see Box 25-1) and Cockayne s syndrome, which is characterized by arrested growth, photosensitivity, and neurological disorders. ... 

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