MECHANISTIC INSIGHTS INTO GENOME STABILITY MAINTENANCE THROUGH COORDINATED DNA REPAIR PATHWAYS

Abstract

Background: To survive and prevent genetic diseases, cells need to maintain genome stability. Ongoing targeting of DNA by normal metabolic processes and external elements dictates the need to have efficient and coordinated repair processes.

Objective: In this study, the authors seek to examine the mechanistic orchestration of key DNA repair systems base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), homologous recombination (HR) and non-homologous end joining (NHEJ) to the integrity of the genome.

Methodology: Human cell models, subjected to oxidative stress and UV-damage were subjected to experimental analyses. Molecular assays and sequencing-based analysis were performed to determine repair performance and interactions between repair pathways.

Findings: The repair efficiency of HR was highest (88%), NER (82%), and BER (78%). NHEJ was found to have as quick repair but less precise (70%). The interactions between pathways were coordinated which enhanced the efficiency of the entire repair by about 1520 percent and minimized considerably the mutation rates.

Conclusion: Coordinated DNA repair pathways is an important mechanism in the maintenance of genome stability. When several repair mechanisms are combined it not only increases the efficiency and accuracy but it also offers valuable knowledge towards therapeutic strategies to counter genomic instability.