Abstract
Long-term shift work is widely believed to increase the risk of certain cancers, but conflicting findings between studies render this association unclear. Evidence of interplay between the circadian clock, cell cycle regulation, and DNA damage detection machinery suggests the possibility that circadian rhythm disruption consequent to shift work could alter the DNA double-strand break (DSB) repair pathway usage to favor mutagenic non-homologous end-joining (NHEJ) repair. To test this hypothesis, we compared relative usage of NHEJ and single-strand annealing (SSA) repair of a complementary ended chromosomal double-stranded break using the Repair Reporter 3 (Rr3) system in Drosophila between flies reared on 12:12 and 8:8 (simulated shift work) light:dark schedules. Actimetric analysis showed that the 8:8 light:dark schedule effectively disrupted the rhythms in locomotor output. Inaccurate NHEJ repair was not a frequent outcome in this system overall, and no significant difference was seen in the usage of NHEJ or SSA repair between the control and simulated shift work schedules. We conclude that this circadian disruption regimen does not alter the usage of mutagenic NHEJ DSB repair in the Drosophila male pre-meiotic germline, in the context of the Rr3 system.
Highlights
Engagement in shift work that involves light during subjective night has been identified as a probable carcinogen [1]
A recent combined prospective study and meta-analysis failed to support an association between shift work and breast cancer [7], and another recent study failed to support a link between night-shift work and prostate cancer [8]
The most immediate effect of night-shift work is the disruption of the circadian rhythm by exposure to light during subjective night, inconsistent sleep schedules, and irregular mealtimes
Summary
Engagement in shift work that involves light during subjective night has been identified as a probable carcinogen [1]. Long-term shift workers have been suggested to be at heightened risk for cancers of the breast [2] (reviewed in [3,4]), prostate [5], and colon [6]. Potential direct mechanistic links have been identified between circadian rhythm disruption and tumor promotion, including increased expression of oncogenes [12], altered levels of inflammation-associated proteins [13,14], and disruption of the cell cycle (reviewed in [15]). A prominent indirect mechanistic link between long-term shift work and tumor promotion is increased obesity [17,18,19,20] and metabolic syndrome [17,21,22].
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