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...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2015-09, Vol.5 (1), p.13752-13752, Article 13752
Main Authors: Manzella, Nicola, Bracci, Massimo, Strafella, Elisabetta, Staffolani, Sara, Ciarapica, Veronica, Copertaro, Alfredo, Rapisarda, Venerando, Ledda, Caterina, Amati, Monica, Valentino, Matteo, Tomasetti, Marco, Stevens, Richard G, Santarelli, Lory
Format: Article
Language:English
Subjects:
Adaptation, Physiological - physiology
Adult
Base excision repair
BMAL1 protein
Circadian rhythm
Circadian Rhythm - physiology
Circadian rhythms
CLOCK Proteins - metabolism
Deoxyribonucleic acid
DNA
DNA damage
DNA Damage - physiology
DNA glycosylase
DNA Glycosylases - metabolism
DNA repair
DNA Repair - physiology
Enzyme Activation
Female
Fibroblasts
Gene Expression Regulation - physiology
Guanine - analogs & derivatives
Guanine - metabolism
Humans
Lymphocytes
Male
OGG1 protein
Workers
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep13752