MUTYH protects telomeres from chronic oxidative damage in cancer cells
Targeted base excision repair prevents telomere loss and mutations caused by oxidized guanine lesions without halting cell proliferation.
In human HeLa cancer cells, researchers used a chemoptogenetic system to induce targeted 8-oxoguanine lesions specifically at telomeres. They investigated how the base excision repair enzyme MUTYH influences chromosome stability under chronic oxidative stress. The team found that MUTYH is required to prevent telomere shortening, telomere loss, and genomic instability. Damaged telomeres in MUTYH-deficient cells did not cause sustained DNA damage signaling or reduce cell proliferation. Whole-genome sequencing revealed an enrichment of G to T transversions in telomeric repeats lacking MUTYH. Combined loss of MUTYH and OGG1 rescued these telomere defects, indicating that single-strand break intermediates from repair drive the instability. Repair-proficient cells rapidly accumulated and resolved these breaks, while glycosylase-deficient cells exhibited breaks only at later time points.
Why it matters
Oxidative stress and telomere attrition are major drivers of cellular aging and genomic decline. Pinpointing how specific base excision repair enzymes handle telomeric oxidative lesions reveals how cells maintain chromosome ends during repeated stress.
Caveats
The experiments were conducted exclusively in cultured HeLa cancer cells using an artificial damage system, so the findings may not directly reflect repair mechanisms in non-malignant primary tissues.
- Genomic instability
- Telomere attrition
- DNA repair
- Oxidative stress and ROS signalling
- Telomerase and telomere maintenance
- MUTYH
- OGG1
- Cancer
- 8-oxoguanine
- Homo sapiens
The paper
MUTYH Activity Maintains Telomere Stability in Response to Chronic Telomeric 8-Oxoguanine Damage in Cancer Cells
De Rosa M, Heidenreich TM, Childs L et al.
Biomolecules · 26 Aug 2026