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Consider this before you jet off to a sunny island for midwinter holiday. Researchers at the University of North Carolina and NC State University have shown a link between time of day of UV exposure and the likelihood of developing skin cancer.

Contrary to what the poorly pigmented among us might expect, the link shown here is not related to greater intensity of UV rays at midday, but to our own circadian clock’s control over DNA damage repair.

That a link exists between the circadian circuitry and onset of other adverse health events, such as asthma and heart attacks, is well known. And studies of mouse liver and brain tissue by other UNC researchers have shown in recent years that the core molecular circadian clock controls the protein XPA (xeroderma pigmentosum group A), which is involved in DNA damage repair (PNAS, Feb 24, 2009; PNAS, March 16, 2010).

In “Control of skin cancer by the circadian rhythm,” (PNAS, Nov 15, 2011), Shobhan Gaddameedhi and colleagues explain that “UV radiation produces two major lesions in DNA … thought to be the primary cause of skin cancer in humans.” A process known as nucleotide excision repair removes the lesions, and the aforementioned circadian-controlled XPA is one of six crucial factors in that process.

Through experiments on hairless mice, the authors showed that the same UV dose is more carcinogenic in hours of the day when the animal’s circadian rhythm slows down nucleotide excision repair. For nocturnal mice, DNA repair activity is at its slowest in the wee hours of the morning, when DNA replication, conversely, is at its most aggressive. Exposure to UVR between 4am and 6am led to a higher frequency of cancer development among the research animals. The authors say the findings imply that, for diurnal humans, afternoon sun exposure is likely more highly carcinogenic.

According to F1000 evaluator Bruce Demple, who rates the paper a “must-read”:

The most striking result in the paper shows that UV-induced skin cancer occurs about 5-fold more frequently when the UV exposure occurs during the time of minimum nucleotide excision repair activity compared to exposure when nucleotide excision repair is maximal.

To be sure, the consequences of total dysfunction of the excision repair genes are known to be severe: skin cancer occurs 5,000 times more frequently on the sun-exposed skin of those who inherit mutations, resulting in the syndrome Xeroderma pigmentosum. But, the authors acknowledge that DNA damage and repair are just two of many factors that impact cancer development and, they note, “cancer is a multistage process and a long-term endpoint of a specific incident.” For the structural biology and cancer research communities, they recommend further studies with repair-deficient and clock mutant animals to “deconvolute the relative contributions of the various pathways to the rhythmicity of the carcinogenic effect of UVR.”

Their recommendation for the rest of us? If you must sunbathe, get it out of the way early in the morning, when your body’s repair capacity is at its best.