Oxidative Damage and DNA Repair Mechanisms in Cancer Cells

Reactive oxygen species (ROS) are by-products of cellular metabolism and external insults, and their accumulation can inflict oxidative lesions on DNA and nucleotide pools. Among these lesions, 8-oxo-7,8-dihydroguanine in DNA or its triphosphate form in the nucleotide pool is particularly mutagenic, provoking G→T transversions. Cancer cells, which often exhibit elevated ROS levels due to oncogenic signalling and metabolic reprogramming, face a dual challenge: ROS-driven genomic instability fuels tumour evolution, yet excessive damage triggers cell death. To counteract this threat, cells deploy multiple layers of defence. At the nucleotide-pool level, NUDIX hydrolases such as MTH1 hydrolyse oxidised dNTPs, preventing their misincorporation. In DNA, excision pathways orchestrated by glycosylases—including OGG1 and MUTYH—recognise and remove oxidised bases, initiating base excision repair (BER). Coordination between these systems maintains genomic integrity, but cancer cells often co-opt or upregulate repair mechanisms to tolerate high oxidative stress. Inhibiting key sanitising enzymes or repair factors therefore represents an attractive therapeutic strategy to drive cancer cells beyond a tolerable damage threshold, induce synthetic lethality with existing treatments and improve patient outcomes.

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Oxidative Damage and DNA Repair Mechanisms in Cancer Cells publication trend

The graph below shows the total number of articles in oxidative damage and dna repair mechanisms in cancer cells across all publications each year (not limited to Nature Index journals).

Technical terms

Reactive oxygen species (ROS): Chemically reactive molecules containing oxygen that can oxidise DNA bases and sugars, leading to mutagenic lesions.

8-oxo-7,8-dihydroguanine (8-oxoG): An oxidised form of guanine that induces G→T transversions if not removed from DNA by repair enzymes.

Nucleotide-pool sanitisation: The hydrolysis of oxidised nucleoside triphosphates (e.g., by MTH1) to prevent their incorporation into DNA.

Base excision repair (BER): A multi-step pathway in which DNA glycosylases remove damaged bases, followed by end processing and gap filling to restore DNA integrity.

Pyrimidine salvage: The metabolic recycling of nucleobases or nucleosides (e.g., via NUDT22) to maintain adequate dNTP pools under stress conditions.

References

1. Visualization of oxidized guanine nucleotides accumulation in living cells with split MutT. Nucleic Acids Research (2024).
2. Exploring MTH1 inhibitory potential of Thymoquinone and Baicalin for therapeutic targeting of breast cancer. Biomedicine & Pharmacotherapy (2024).
3. NUDT22 promotes cancer growth through pyrimidine salvage. Oncogene (2023).
4. Cellular Levels of 8-Oxoguanine in either DNA or the Nucleotide Pool Play Pivotal Roles in Carcinogenesis and Survival of Cancer Cells. International Journal of Molecular Sciences (2014).