TitleCatalytic activity of OGG1 is impaired by Zinc deficiency.
Publication TypeJournal Article
Year of Publication2024
AuthorsSharma P, Wong CP, Ho E, Sampath H
JournalDNA Repair (Amst)
Date Published2024 Feb
KeywordsAnimals, DNA, DNA Damage, DNA Glycosylases, DNA Repair, Mice, Oxidative Stress, Zinc

Oxidative stress-induced DNA base modifications, if unrepaired, can increase mutagenesis and genomic instability, ultimately leading to cell death. Cells predominantly use the base excision repair (BER) pathway to repair oxidatively-induced non-helix distorting lesions. BER is initiated by DNA glycosylases, such as 8-oxoguanine DNA glycosylase (OGG1), which repairs oxidatively modified guanine bases, including 7,8-dihydro-8-oxoguanine (8-oxoG) and ring-opened formamidopyrimidine lesions, 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG). The OGG1 protein contains a C2H2 zinc (Zn) finger DNA binding domain. However, the impact of dietary Zn deficiency on OGG1 catalytic activity has not been extensively studied. Zn is a common nutrient of concern with increasing age, and the prevalence of oxidative DNA damage is also concurrently increased during aging. Thus, understanding the potential regulation of OGG1 activity by Zn is clinically relevant. The present study investigates the impact of a range of Zn statuses, varying from severe Zn deficiency to exogenous Zn-supplementation, in the context of young and aged animals to determine the impact of dietary Zn-status on OGG1 activity and oxidative DNA damage in mice. Our findings suggest that nutritional Zn deficiency impairs OGG1 activity and function, without altering gene expression, and that aging further exacerbates these effects. These results have important implications for nutritional management of Zn during aging to mitigate age-associated DNA damage.

Alternate JournalDNA Repair (Amst)
PubMed ID38228016
PubMed Central IDPMC10851324
Grant ListK99 DK100640 / DK / NIDDK NIH HHS / United States
P30 ES030287 / ES / NIEHS NIH HHS / United States
R00 DK100640 / DK / NIDDK NIH HHS / United States