2026-10-06T21:38:23Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34073284 2026-10-05T17:46:44Z category_1 category_4 category_8 category_12 category_13 category_14 category_24 category_64 category_132 category_134 portal_5 item_type_3 month_year_10_2026

<p>Yeast strains used in this study.</p> Yang Sui (29617) Dao-Qiong Zheng (14509715) Yeke Wang (11492611) Shan-Shan Zhao (820926) Ke-Jing Li (23589005) Cunqi Ye (12516868) Ke Zhang (115386) Biophysics Biochemistry Microbiology Cell Biology Genetics Molecular Biology Evolutionary Biology Cancer Infectious Diseases Virology transversions &# 8212 single nucleotide variations genome sequencing uncovered eukaryotic genome remains decoupling metabolic defense amyotrophic lateral sclerosis sod1 deficiency sculpts unlike yeast sod1 fold ), loss fold ), yeast model fold increase whereas others thus preventing staggering 48 sole executioner remain benign recombinational chaos oxoguanine overproduction molecular fingerprint mediated excision long recognized indispensable guardian highly resistant genomic storm genomic integrity genomic instability frontline antioxidant findings provide enzyme function dramatic surge created equal concerted actions completely abolished broader role binding sites associated variants anaerobic conditions absence unleashes <div><p>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.</p></div> 2026-10-05T17:46:41Z Dataset Dataset 10.1371/journal.pgen.1012326.s002 https://figshare.com/articles/dataset/_p_Yeast_strains_used_in_this_study_p_/34073284 CC BY 4.0