Authors
Yang Sui, Dao-Qiong Zheng, Yeke Wang, Shan-Shan Zhao, Ke-Jing Li, Cunqi Ye, Ke Zhang
Published in
PLoS genetics. Volume 22. Issue 10. Pages e1012326. Oct 05, 2026. Epub Oct 05, 2026.
Abstract
Superoxide dismutase 1 (Sod1) is long recognized as a frontline antioxidant, yet its broader role in safeguarding the eukaryotic genome remains under-explored. Here, using a yeast model, we reveal that Sod1 is an indispensable guardian of genomic integrity. Its absence unleashes a genomic storm: whole-genome sequencing uncovered a dramatic surge in single nucleotide variations (13-fold), loss of heterozygosity (12-fold), chromosomal rearrangements (4-fold), and a staggering 48-fold increase in aneuploidy. Remarkably, this genomic instability was completely abolished under anaerobic conditions, identifying reactive oxygen species as the sole executioner. We demonstrate that Sod1 deficiency sculpts a unique mutational landscape dominated by C:G to A:T transversions-a molecular fingerprint of 8-oxoguanine overproduction. Mechanistically, these lesions are exacerbated by error-prone DNA polymerase ζ but mitigated by the concerted actions of Ogg1-mediated excision and DNA polymerase η. Critically, we show that Amyotrophic Lateral Sclerosis-associated variants are not created equal: the H48Q mutation shatters genome stability, whereas others (A4V, G36R, and G93A) remain benign in this context. Unlike yeast Sod1, human Sod1 is highly resistant to amino acid substitutions outside copper-binding sites, thus preventing the loss of enzyme function. Overall, our findings provide a mechanistically framework for understanding how Sod1 dysfunction drives genome instability in eukaryotic cells.
PMID:
42832558
Bibliographic data and abstract were imported from PubMed on 06 Oct 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 18
- Comments 0