Circadian Modulation of 8-Oxoguanine DNA Damage Repair.
The DNA base excision repair pathway is the main system involved in the removal of oxidative damage to DNA such as 8-Oxoguanine (8-oxoG) primarily via the 8-Oxoguanine DNA glycosylase (OGG1). Our goal was to investigate whether the repair of 8-oxoG DNA damage follow a circadian rhythm. In a group of 15 healthy volunteers, we found a daily variation of Ogg1 expression and activity with higher levels in the morning compared to the evening hours. Consistent with this, we also found lower levels of 8-oxoG in morning hours compared to those in the evening hours. Lymphocytes exposed to oxidative damage to DNA at 8:00 AM display lower accumulation of 8-oxoG than lymphocytes exposed at 8:00 PM. Furthermore, altered levels of Ogg1 expression were also observed in a group of shift workers experiencing a deregulation of circadian clock genes compared to a control group. Moreover, BMAL1 knockdown fibroblasts with a deregulated molecular clock showed an abolishment of circadian variation of Ogg1 expression and an increase of OGG1 activity. Our results suggest that the circadian modulation of 8-oxoG DNA damage repair, according to a variation of Ogg1 expression, could render humans less susceptible to accumulate 8-oxoG DNA damage in the morning hours.
Occupational Medicine, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Via Tronto 10/A, 60126 Ancona, Italy.
Nicola
N
Manzella
Occupational Medicine, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Via Tronto 10/A, 60126 Ancona, Italy.
Massimo
M
Bracci
Occupational Medicine, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Via Tronto 10/A, 60126 Ancona, Italy.
Elisabetta
E
Strafella
Occupational Medicine, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Via Tronto 10/A, 60126 Ancona, Italy.
Sara
S
Staffolani
Occupational Medicine, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Via Tronto 10/A, 60126 Ancona, Italy.
Veronica
V
Ciarapica
Healthcare Workers Service, ASUR Area 2, Loreto Hospital, Via S. Francesco 1, 60025 Loreto, Italy.
Alfredo
A
Copertaro
Section of Occupational Medicine, Department of Internal Medicine and Systemic Diseases, University of Catania, Via Santa Sofia 78, 95123 Catania, Italy.
Venerando
V
Rapisarda
Hygiene and Public Health, Department "G.F. Ingrassia", University of Catania, Via Santa Sofia 87, 95123 Catania, Italy.
Caterina
C
Ledda
Occupational Medicine, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Via Tronto 10/A, 60126 Ancona, Italy.
Monica
M
Amati
Occupational Medicine, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Via Tronto 10/A, 60126 Ancona, Italy.
Matteo
M
Valentino
Occupational Medicine, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Via Tronto 10/A, 60126 Ancona, Italy.
Marco
M
Tomasetti
Department of Community Medicine, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-6325, USA.
Richard G
RG
Stevens
Occupational Medicine, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Via Tronto 10/A, 60126 Ancona, Italy.
Lory
L
Santarelli
D000222:Adaptation, Physiological / Q000502:physiology*; D000328:Adult; D056926:CLOCK Proteins / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology*; D004249:DNA Damage / Q000502:physiology*; D045647:DNA Glycosylases / Q000378:metabolism*; D004260:DNA Repair / Q000502:physiology*; D004789:Enzyme Activation; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D008297:Male
C024829:8-hydroxyguanine; D006147:Guanine; D056926:CLOCK Proteins; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human