Synergistic interactions between XPC and p53 mutations in double-mutant mice: neural tube abnormalities and accelerated UV radiation-induced skin cancer

• Published in: Current biology Vol. 6; no. 12; pp. 1691 - 1694
• Main Authors: Cheo, David L., Meira, Lisiane B., Hammer, Robert E., Burns, Dennis K., Doughty, Ana T.B., Friedberg, Errol C.
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.12.1996
• Subjects: Animals; DNA Repair; DNA-Binding Proteins - genetics; Female; Gene Expression Regulation; Humans; Male; Mice; Mutagenesis; Neural Tube Defects; Skin Neoplasms - genetics; Skin Neoplasms - pathology; Tumor Suppressor Protein p53 - genetics; Ultraviolet Rays; Xeroderma Pigmentosum - genetics
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/S0960-9822(02)70794-X

The significance of DNA repair to human health has been well documented by studies on xeroderma pigmentosum (XP) patients, who suffer a dramatically increased risk of cancer in sun-exposed areas of their skin [1,2]. This autosomal recessive disorder has been directly associated with a defect in nucleotide excision–repair (NER) [1,2]. Like human XP individuals, mice carrying homozygous mutations in XP genes manifest a predisposition to skin carcinogenesis following exposure to ultraviolet (UV) radiation [3–5]. Recent studies have suggested that, in addition to roles in apoptosis [6] and cell-cycle checkpoint control [7] in response to DNA damage, p53 protein may modulate NER [8]. Mutations in the p53 gene have been observed in 50% of all human tumors [9] and have been implicated in both the early [10] and late [11] stages of skin cancer. To examine the consequences of a combined deficiency of the XPC and the p53 proteins in mice, we generated double-mutant animals. We document a spectrum of neural tube defects in XPC p53 mutant embryos. Additionally, we show that, following exposure to UV-B radiation, XPC p53 mutant mice have more severe solar keratosis and suffer accelerated skin cancer compared with XPC mutant mice that are wild-type with respect to p53.