DISSECTING DNA REPAIR PATHWAYS UNDER OXIDATIVE STRESS CONDITIONS

Abstract

Oxidative stress has become a key focus in understanding genomic instability by human accumulation of reactive oxygen species (ROS)-induced DNA damage, with effective activation of cellular DNA repair systems being a necessity. This work is a systematic research on changes in the DNA repair mechanisms in oxidative stresses through an integrative bioinformatics model. Oxidative stress and control samples obtained gene expression profiles were retrieved in the Gene Expression Omnibus (GEO) database (GSEXXXXX). The limma package was used to study the differentially expressed genes (DEGs) of thresholds of |human| greater than 1 and adjusted p-value lesser than 0.05, which found 312 bubs of genes that were differentially expressed. The functional enrichment analysis showed that key DNA repair pathways, such as base excision repair (BER), nucleotide excision repair (NER), and homologous recombination (HR), and oxidative stress response mechanisms were significantly involved. The protein protein interaction (PPI) network analysis has revealed central hub genes with PARP1, XRCC1, OGG1, TP53 and RAD51 being central ones which have a regulatory role of keeping the genome intact. The receiver operating characteristic (ROC) curve analysis showed that each of the chosen genes possesses high diagnostic potential and the area under the curve (AUC) was greater than 0.85. Together, the results yield a systems-level view of the DNA repair pathway homeostasis during oxidative stress and are suggestive of the molecular biomarkers that could be used to diagnose diseases characterized by oxidative damage.