Premium
Night shift schedule causes circadian dysregulation of DNA repair genes and elevated DNA damage in humans
Author(s) -
Koritala Bala S. C.,
Porter Kenneth I.,
Arshad Osama A.,
Gajula Rajendra P.,
Mitchell Hugh D.,
Arman Tarana,
Manjanatha Mugimane G.,
Teeguarden Justin,
Van Dongen Hans P. A.,
McDermott Jason E.,
Gaddameedhi Shobhan
Publication year - 2021
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/jpi.12726
Subject(s) - circadian rhythm , shift work , biology , dna repair , dna damage , transcriptome , circadian clock , clock , endocrinology , gene , medicine , genetics , dna , neuroscience , gene expression
Abstract Circadian disruption has been identified as a risk factor for health disorders such as obesity, cardiovascular disease, and cancer. Although epidemiological studies suggest an increased risk of various cancers associated with circadian misalignment due to night shift work, the underlying mechanisms have yet to be elucidated. We sought to investigate the potential mechanistic role that circadian disruption of cancer hallmark pathway genes may play in the increased cancer risk in shift workers. In a controlled laboratory study, we investigated the circadian transcriptome of cancer hallmark pathway genes and associated biological pathways in circulating leukocytes obtained from healthy young adults during a 24‐hour constant routine protocol following 3 days of simulated day shift or night shift. The simulated night shift schedule significantly altered the normal circadian rhythmicity of genes involved in cancer hallmark pathways. A DNA repair pathway showed significant enrichment of rhythmic genes following the simulated day shift schedule, but not following the simulated night shift schedule. In functional assessments, we demonstrated that there was an increased sensitivity to both endogenous and exogenous sources of DNA damage after exposure to simulated night shift. Our results suggest that circadian dysregulation of DNA repair may increase DNA damage and potentiate elevated cancer risk in night shift workers.