Mechanisms of oncogene-induced replication stress: jigsaw falling into place

Research output: Contribution to journalReview articlepeer-review

Authors

Colleges, School and Institutes

External organisations

  • The Francis Crick Institute

Abstract

Oncogene activation disturbs cellular processes and accommodates a complex landscape of changes in the genome that contribute to genomic instability, which accelerates mutation rates and promotes tumorigenesis. Part of this cellular turmoil involves deregulation of physiologic DNA replication, widely described as replication stress. Oncogene-induced replication stress is an early driver of genomic instability and is attributed to a plethora of factors, most notably aberrant origin firing, replication-transcription collisions, reactive oxygen species, and defective nucleotide metabolism.

Significance: Replication stress is a fundamental step and an early driver of tumorigenesis and has been associated with many activated oncogenes. Deciphering the mechanisms that contribute to the replication stress response may provide new avenues for targeted cancer treatment. In this review, we discuss the latest findings on the DNA replication stress response and examine the various mechanisms through which activated oncogenes induce replication stress.

Details

Original languageEnglish
Pages (from-to)537-555
Number of pages19
JournalCancer Discovery
Volume8
Issue number5
Early online date13 Apr 2018
Publication statusPublished - May 2018

Keywords

  • DNA replication stress , oncogenes , genomic instability , cancer