Work

Mechanisms of Oncogene-Induced Replication Stress: Jigsaw Falling into Place

Year: 2018

Type: review

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. Cancer Discov; 8(5); 537–55. ©2018 AACR.

Source: Cancer Discovery

DOI: 10.1158/2159-8290.cd-17-1461

Authors: Panagiotis Kotsantis, Eva Petermann, Simon J. Boulton

Institutions: The Francis Crick Institute, University of Birmingham

Language: English

Topic: DNA Repair Mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Wellcome Trust, Francis Crick Institute, Cancer Research UK