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

David L. Cheo, Lisiane B. Meira, Robert E Hammer, Dennis K Burns, Ana T B Doughty, Errol C Friedberg

Research output: Contribution to journalArticle

61 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1691-1694
Number of pages4
JournalCurrent Biology
Issue number12
StatePublished - Dec 1996


ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

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