DNA replication stress: oncogenes in the spotlight

Abstract

Precise replication of genetic material is essential to maintain genome stability. DNA replication is a tightly regulated process that ensues faithful copies of DNA molecules to daughter cells during each cell cycle. Perturbation of DNA

replication may compromise the transmission of genetic information, leading to DNA damage, mutations, and chro- mosomal rearrangements. DNA replication stress, also referred to as DNA replicative stress, is defined as the slow- ing or stalling of replication fork progression during DNA synthesis as a result of different insults. Oncogene

activation, one hallmark of cancer, is able to disturb numerous cellular processes, including DNA replication. In fact, extensive work has indicated that oncogene-induced replication stress is an important source of genomic instability in human carcinogenesis. In this review, we focus on main oncogenes that induce DNA replication stress, such as RAS, MYC, Cyclin E, MDM2, and BCL-2 among others, and the molecular mechanisms by which these oncogenes interfere with normal DNA replication and promote genomic instability.