The Role of DNA Replication in Maintaining Genetic Stability

Abstract

DNA replication is an essential biological process that allows genetic information to be accurately transmitted from one cell generation to the next. Because even small replication errors can become permanent mutations, cells have evolved multiple mechanisms to maintain replication fidelity. These include accurate nucleotide selection by DNA polymerases, polymerase proofreading, post-replicative mismatch repair, and coordinated protection of replication forks. Reviews of replication fidelity show that DNA polymerase selectivity, 3′–5′ exonucleolytic proofreading, and mismatch repair operate together to keep mutation rates low. This paper examines the role of DNA replication in genetic stability, focusing on the replication process, polymerase fidelity, proofreading, mismatch repair, replication-fork stability, chromosomal integrity, mutation prevention, disease implications, and future research. Understanding these mechanisms is important because defects in replication fidelity and repair can contribute to genomic instability and human disease, including cancer.