Control of skin cancer by the circadian rhythm

Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):18790-5. doi: 10.1073/pnas.1115249108. Epub 2011 Oct 24.


Skin cancer is the most common form of cancer in the United States. The main cause of this cancer is DNA damage induced by the UV component of sunlight. In humans and mice, UV damage is removed by the nucleotide excision repair system. Here, we report that a rate-limiting subunit of excision repair, the xeroderma pigmentosum group A (XPA) protein, and the excision repair rate exhibit daily rhythmicity in mouse skin, with a minimum in the morning and a maximum in the afternoon/evening. In parallel with the rhythmicity of repair rate, we find that mice exposed to UV radiation (UVR) at 4:00 AM display a decreased latency and about a fivefold increased multiplicity of skin cancer (invasive squamous cell carcinoma) than mice exposed to UVR at 4:00 PM. We conclude that time of day of exposure to UVR is a contributing factor to its carcinogenicity in mice, and possibly in humans.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / etiology
  • Carcinoma, Squamous Cell / physiopathology*
  • Circadian Rhythm / physiology*
  • DNA Damage
  • DNA Repair
  • Disease Models, Animal
  • Humans
  • Immunohistochemistry / methods
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Skin / radiation effects*
  • Skin Neoplasms / etiology
  • Skin Neoplasms / physiopathology*
  • Sunlight
  • Time Factors
  • Xeroderma Pigmentosum Group A Protein / biosynthesis
  • Xeroderma Pigmentosum Group A Protein / genetics*


  • Xeroderma Pigmentosum Group A Protein
  • Xpa protein, mouse