The Role of DNA Replication Errors and Defects in Repair Systems in the Development of Genetic Diseases

Maintaining genome stability is a fundamental prerequisite for cell survival and the accurate transmission of genetic information to future generations. DNA replication, as the central process responsible for this transmission, is inherently error-prone despite the high fidelity of DNA polymerase enzymes. Various factors, including abnormal DNA structures, repetitive sequences, and replication stress, can lead to the stalling or collapse of replication forks and the generation of molecular errors. In this review article, by examining up-to-date scientific resources, the mechanisms of replication error generation, the role of specialized repair systems including Mismatch Repair (MMR), Base Excision Repair (BER), Nucleotide Excision Repair (NER), and Homologous Recombination (HR), as well as DNA damage tolerance pathways in maintaining genome integrity, have been investigated. The findings indicate that repair systems, acting as a secondary line of defense, play a vital role in correcting errors that escape polymerase quality control, and defects in any of these pathways, depending on the tissue type and the nature of the affected gene, lead to different spectra of genetic diseases, ranging from hereditary neurodegenerative disorders caused by defects in single-strand break repair to hereditary cancers such as Lynch syndrome and BRCA-associated cancers. The results of this review emphasize that genome stability is the product of a precise balance between the replication process and the repair network, and disruption of this balance contributes to genomic instability and disease development. A deeper understanding of these mechanisms can pave the way for the development of targeted therapeutic strategies for genetic diseases

کلیدواژه ها:

DNA replication ، DNA repair ، genome instability ، genetic diseases ، replication stress ، mutation