Cited by 416DNA Repair MechanismsCancer-related Molecular PathwaysTelomeres, Telomerase, and Senescence

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

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Kotsantis, Panagiotis, Petermann, Eva, Boulton, Simon J.·2018·Cancer Discovery

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.

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  • DNA damage is responsible for oncogene-induced senescence, which involves replication stress and subsequent double-strand breaks from hyper-replication associated with activated oncogenes.

    “DNA damage is also responsible for oncogene-induced senescence, which involves replication stress and subsequent DSBs as the consequence of hyper-replication associated with activated oncogenes68.”

    From The central role of DNA damage in the ageing process (2021) · cites this paper as [68]

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Research works printed but not linked: 5

  1. [14]Feijoo C Hall-Jackson C Wu R Jenkins D Leitch J Gilbert DM Activation of mammalian Chk1 during DNA replication arrest: a role for Chk1 in the intra-S phase checkpoint monitoring replication origin firing J Cell Biol 2001 154 913 23 11535615 PMC1255922
  2. [38]Kotsantis P Jones RM Higgs MR Petermann E Cancer therapy and replication stress: forks on the road to perdition Adv Clin Chem 2015 69 91 138 25934360
  3. [50]Sanjiv K Hagenkort A Calderon-Montano JM Koolmeister T Reaper PM Mortusewicz O Cancer-Specific Synthetic Lethality between ATR and CHK1 Kinase Activities Cell Rep 2016 17 3407 16 PMC5638787 28009306
  4. [98]Jones RM Mortusewicz O Afzal I Lorvellec M Garcia P Helleday T Increased replication initiation and conflicts with transcription underlie Cyclin E-induced replication stress Oncogene 2013 32 3744 53 22945645
  5. [199]Vafa O Wade M Kern S Beeche M Pandita TK Hampton GM c-Myc can induce DNA damage, increase reactive oxygen species, and mitigate p53 function: a mechanism for oncogene-induced genetic instability Mol Cell 2002 9 1031 44 12049739

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Authors
Kotsantis, P., Petermann, E., & Boulton, S. J.
Affiliations
  • The Francis Crick Institute (GB)
  • University of Birmingham (GB)
Corresponding author
Kotsantis, Panagiotis
Venue
Cancer Discovery
Published
2018-04-30
Volume
8
Issue
5
Pages
537-555
ISSN
  • 2159-8274 (ISSN-L)
  • 2159-8290
OpenAlex
W2797725119
Cited by
416
References
232
Citations by year
2026: 43 · 2025: 55 · 2024: 41 · 2023: 59 · 2022: 53 · 2021: 63 · 2020: 58 · 2019: 33 · 2018: 11
FWCI
4.05
Type
journal article
Language
en
Open access
Locations
  • Cancer Discovery (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Lancaster EPrints (Lancaster University) (submittedVersion)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
Funders
  • Wellcome Trust (FC0010048, 104558/Z/14/Z)
  • Francis Crick Institute (10048)
  • Cancer Research UK (FC0010048)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
Keywords
oncogene-induced replication stress, genomic instability, carcinogenesis, replication origin firing, reactive oxygen species, nucleotide metabolism, cancer therapy targets
MeSH terms
Animals, Antineoplastic Agents, Cell Cycle, Cell Transformation, Neoplastic, DNA Damage, DNA Replication, DNA-Binding Proteins, Gene Expression Regulation, Humans, Mutation, Neoplasms, Oncogenes, Oxidation-Reduction, Stress, Physiological, Transcription, Genetic, Signal Transduction, Reactive Oxygen Species, Replication Origin, Genomic Instability, Molecular Targeted Therapy

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