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Base excision repair within structure-forming repeat sequences and its impact on cancer and other diseases
Journal article   Open access   Peer reviewed

Base excision repair within structure-forming repeat sequences and its impact on cancer and other diseases

Carson B Cohen, Millie C Coombes, Christopher P Merlo, Chantal A Kontor, Riaz Meah and Amy M Whitaker
NAR cancer, v 7(4), zcaf051
01 Dec 2025
PMID: 41415328
url
https://doi.org/10.1093/narcan/zcaf051View
Published, Version of Record (VoR) Open

Abstract

Manipulating DNA repair and the DNA damage response to improve cancer therapy
Oxidative DNA damage is a major driver of genome instability and human disease. Among the various types of oxidative DNA base lesions, 8-oxo-7,8-dihydroguanine (8oxoG) is particularly prevalent due to guanine’s low oxidation potential and the abundance of guanine-rich (G-rich) sequences across the genome. Structure-forming repeat sequences, which are commonly G-rich, can adopt alternative DNA secondary structures that further expose nucleobases to oxidative damage. The base excision repair (BER) pathway is primarily responsible for the repair of 8oxoG lesions; however, the complex topologies and dynamic conformations formed by these repeat sequences present challenges for complete repair. Inefficient BER within these structures can lead to DNA strand breaks, mutations, and large chromosomal rearrangements, all of which are associated with human disease. Notably, structure-forming repeat sequences are often enriched at regulatory genomic regions, where BER can directly influence processes such as replication and transcription. This review summarizes current insights into BER activity within oxidatively damaged structure-forming repeat sequences and highlights how repair efficiency within these sequences impacts genome stability and disease. Graphical Abstract

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Collaboration types
Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
Oncology
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