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

Curr Biol. 1996 Dec 1;6(12):1691-4. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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*


  • DNA-Binding Proteins
  • Tumor Suppressor Protein p53
  • Xpc protein, mouse
  • XPC protein, human