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

Panagiotis Kotsantis; Eva Petermann; Simon J. Boulton

doi:10.1158/2159-8290.CD-17-1461

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

Panagiotis Kotsantis
, Eva Petermann
, Simon J. Boulton

Cancer and Genomic Sciences

Research output: Contribution to journal › Review article › peer-review

101 Citations (Scopus)

474 Downloads (Pure)

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.

Original language	English
Pages (from-to)	537-555
Number of pages	19
Journal	Cancer Discovery
Volume	8
Issue number	5
Early online date	13 Apr 2018
DOIs	https://doi.org/10.1158/2159-8290.CD-17-1461
Publication status	Published - May 2018

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

DNA replication stress
oncogenes
genomic instability
cancer

Access to Document

10.1158/2159-8290.CD-17-1461Licence: None: All rights reserved

Kotsantis_et_al_Mechanisms_of_oncogene-induced_Cancer_Discovery_2018
Published in Cancer Discovery on 13/04/2018 DOI: 10.1158/2159-8290.CD-17-1461 URL: http://cancerdiscovery.aacrjournals.org/content/8/5/537
Accepted author manuscript, 2.08 MBLicence: Other (please specify with Rights Statement)

http://cancerdiscovery.aacrjournals.org/content/8/5/537Licence: None: All rights reserved

101 Citations
2 Poster
2 Article

Increased global transcription activity as a mechanism of oncogene-induced replication stress
Kotsantis, P., Marques Silva, L., Irmscher, S., Jones, R., Folkes, L., Gromak, N. & Petermann, E., Jul 2017.
Research output: Contribution to conference (unpublished) › Poster
Increased global transcription activity as a mechanism of replication stress in cancer
Kotsantis, P., Marques Silva, L., Irmscher, S., Jones, R., Folkes, L., Gromak, N. & Petermann, E., Jun 2016.
Research output: Contribution to conference (unpublished) › Poster
Increased global transcription activity as a mechanism of replication stress in cancer
Kotsantis, P., Marques Silva, L., Irmscher, S., Jones, R., Folkes, L., Gromak, N. & Petermann, E., Dec 2016, In: Nature Communications. 7, 1, 13 p., 13087.
Research output: Contribution to journal › Article › peer-review

Open Access
File
114 Citations (Scopus)

334 Downloads (Pure)
Increased replication initiation and conflicts with transcription underlie Cyclin E-induced replication stress
Jones, R., Mortusewicz, O., Afzal, I., Lorvellec, M., García, P., Helleday, T. & Petermann, E., 2012, In: Oncogene.
Research output: Contribution to journal › Article › peer-review
146 Citations (Scopus)

Interference Between Replication and Transcription as a Mechanism of Oncogene-Induced DNA Damage
Petermann, E. (Principal Investigator)
WORLDWIDE CANCER RESEARCH
1/11/13 → 31/10/16
Project: Research

Cite this

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title = "Mechanisms of oncogene-induced replication stress: jigsaw falling into place",

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.",

keywords = "DNA replication stress , oncogenes , genomic instability , cancer",

author = "Panagiotis Kotsantis and Eva Petermann and Boulton, \{Simon J.\}",

note = "{\textcopyright}2018 American Association for Cancer Research.",

year = "2018",

month = may,

doi = "10.1158/2159-8290.CD-17-1461",

language = "English",

volume = "8",

pages = "537--555",

journal = "Cancer Discovery",

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publisher = "American Association for Cancer Research",

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TY - JOUR

T1 - Mechanisms of oncogene-induced replication stress

T2 - jigsaw falling into place

AU - Kotsantis, Panagiotis

AU - Petermann, Eva

AU - Boulton, Simon J.

PY - 2018/5

Y1 - 2018/5

N2 - 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.

AB - 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.

KW - DNA replication stress

KW - oncogenes

KW - genomic instability

KW - cancer

U2 - 10.1158/2159-8290.CD-17-1461

DO - 10.1158/2159-8290.CD-17-1461

M3 - Review article

C2 - 29653955

SN - 2159-8274

VL - 8

SP - 537

EP - 555

JO - Cancer Discovery

JF - Cancer Discovery

IS - 5

ER -

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

Abstract

UN SDGs

Keywords

Access to Document

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Research output

Increased global transcription activity as a mechanism of oncogene-induced replication stress

Increased global transcription activity as a mechanism of replication stress in cancer

Increased global transcription activity as a mechanism of replication stress in cancer

Increased replication initiation and conflicts with transcription underlie Cyclin E-induced replication stress

Projects

Interference Between Replication and Transcription as a Mechanism of Oncogene-Induced DNA Damage

Cite this