# OGG1 and MUTYH DNA Glycosylases, the Dynamic Duo Against 8-Oxoguanine DNA Lesion: Structure, Regulation, and Novel Emerging Roles

## TL;DR

This paper reviews the roles of OGG1 and MUTYH enzymes in repairing DNA damage caused by 8-oxoguanine, highlighting their structure, regulation, and impact on diseases.

## Contribution

The paper provides a comprehensive review of the structure, regulation, and emerging roles of OGG1 and MUTYH DNA glycosylases.

## Key findings

- OGG1 and MUTYH are essential for repairing 8-oxoguanine lesions in DNA.
- Dysfunction in these enzymes is linked to neurodegenerative diseases, metabolic syndromes, and cancer.
- Regulation of these enzymes is critical to prevent genomic instability and cell death.

## Abstract

OGG1 and MUTYH are base excision repair (BER) DNA glycosylases (DGs) from the Helix–hairpin–Helix superfamily responsible for initiating and coordinating the repair of 8-oxo-7,8-dihydroguanine (OG), and its replication-derived mispair with adenine (OG:A), respectively. The DNA repair activities of these DGs are pivotal to safeguarding nuclear and mitochondrial genomes. Indeed, DG functional impairment is associated with numerous pathologies, including neurodegenerative diseases, metabolic syndromes, and cancer. The timely and precise localization and processing of oxidized nucleobases carried out by these DGs are modulated by a complex regulatory network at both transcriptional and posttranslational levels, as well as intricate protein–protein interaction networks. In the absence of regulation, inappropriate and imbalanced DG activity may trigger telomeric instability, changes in transcriptional profiles and cell death. This review focuses on summarizing key features of OGG1 and MUTYH function, with a special emphasis on structure, regulation, and novel emerging roles.