DNA replication: causes of replication stress and DNA damage response pathways

A review on DNA replication

Abstract

DNA replication is a crucial cellular mechanism that enables proper genetic information to be duplicated and subsequently transferred to the daughter cells. Several perturbations, whether endogenous or external, can impede the accurate advancement and completion of the replication process, endangering genomic integrity, known as replication stress. Secondary DNA structures like alternative non-B form at common fragile sites, oncogenes (RAS, MYC, Cyclin E and CDC6) induction, ribonucleotides (precursors of RNA) incorporation into DNA, RNA:DNA hybrids and other factors have serious implications on cell survival, genome stability and human diseases like carcinogenesis. Cellular DNA damage response as well as DNA repair are crucial for ensuring accurate synthesis of genetic material and preserving genome integrity in case of replication stress. This review aims to highlight the major causes of replication stress as well as the DNA damage response mechanisms that are induced to maintain genomic stability during DNA replication.