DNA REPAIR ENGINEERING APPROACHES TO ENHANCE RESISTANCE AGAINST OXIDATIVE STRESS-INDUCED MUTATIONS

Abstract

Background: Oxidative stress induced by reactive oxygen species (ROS) is a major cause of DNA damage, genomic instability and mutation accumulation in biological systems. Excessive ROS production can cause single-strand breaks, double-strand breaks and oxidative modification of the bases, resulting in cellular dysfunction, aging and disease progression. Natural DNA repair systems are often inefficient under conditions of severe oxidative stress.

Objective: The objective of this work was to investigate DNA repair engineering approaches to improve resistance to oxidative stress-induced mutations and to enhance genomic stability.

Methods: CRISPR/synthetic biology approaches includingEngineered cell models were developed to modulate the Cas-mediated DNA repair pathway, augment base excision repair (BER), engineer homologous recombination and control antioxidant-associated genes. Controlled conditions of exposure to ROS were used to evaluate resistance to oxidative stress, DNA repair efficiency and mutation frequency.

Results: The engineered cells had about 35-42% increase in DNA repair efficiency and 38-45% reduction in oxidative mutation frequency compared to the wild-type cells. Cellular survival under oxidative stress was improved by nearly 30% and ROS-induced DNA strand breaks and chromosomal instability were significantly reduced. Improved genome integrity and cellular protection were attributed to increased BER enzyme activity and antioxidant defense mechanisms.

Conclusion:  DNA repair engineering increases repair efficiency, reduces mutation accumulation and preserves genomic stability, thereby improving resistance to oxidative DNA damage. These approaches hold promising applications in biomedicine, aging research and stress-resistant synthetic biological systems.