Oncogene-induced replication stress drives genome instability and tumorigenesis

Dan Sarni; Batsheva Kerem

doi:10.3390/ijms18071339

Oncogene-induced replication stress drives genome instability and tumorigenesis

Dan Sarni, Batsheva Kerem^*

^*Corresponding author for this work

Department of Genetics

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

19 Scopus citations

Abstract

Genomic instability plays a key role in driving cancer development. It is already found in precancerous lesions and allows the acquisition of additional cancerous features. A major source of genomic instability in early stages of tumorigenesis is DNA replication stress. Normally, origin licensing and activation, as well as replication fork progression, are tightly regulated to allow faithful duplication of the genome. Aberrant origin usage and/or perturbed replication fork progression leads to DNA damage and genomic instability. Oncogene activation is an endogenous source of replication stress, disrupting replication regulation and inducing DNA damage. Oncogene-induced replication stress and its role in cancer development have been studied comprehensively, however its molecular basis is still unclear. Here, we review the current understanding of replication regulation, its potential disruption and how oncogenes perturb the replication and induce DNA damage leading to genomic instability in cancer.

Original language	American English
Article number	1339
Journal	International Journal of Molecular Sciences
Volume	18
Issue number	7
DOIs	https://doi.org/10.3390/ijms18071339
State	Published - Jul 2017

Bibliographical note

Funding Information:
This work was partially supported by grants from the Israel Science Foundation (Grant No. 176/11), Israel Science Foundation (Grant No. 2535/16), The Chief Scientist Office of the Israel Ministry of Health (Grant No. 3-00000-6014), the Israeli Cancer Association (grant No. 20141044), the Israeli centers of research excellence (I-CORE), Gene Regulation in Complex Human Disease, Center Number 41/11, and by the Cooperation Program in Cancer Research of the Deutsches Krebsforschungszentrum (DKFZ) and Israel’s Ministry of Science and Technology (MOST). We thank all members of the Kerem lab for thoughtful discussions

Publisher Copyright:
© 2017 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

Cancer
DNA replication
Genomic instability
Oncogene
Replication stress

UN SDGs

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

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10.3390/ijms18071339

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title = "Oncogene-induced replication stress drives genome instability and tumorigenesis",

abstract = "Genomic instability plays a key role in driving cancer development. It is already found in precancerous lesions and allows the acquisition of additional cancerous features. A major source of genomic instability in early stages of tumorigenesis is DNA replication stress. Normally, origin licensing and activation, as well as replication fork progression, are tightly regulated to allow faithful duplication of the genome. Aberrant origin usage and/or perturbed replication fork progression leads to DNA damage and genomic instability. Oncogene activation is an endogenous source of replication stress, disrupting replication regulation and inducing DNA damage. Oncogene-induced replication stress and its role in cancer development have been studied comprehensively, however its molecular basis is still unclear. Here, we review the current understanding of replication regulation, its potential disruption and how oncogenes perturb the replication and induce DNA damage leading to genomic instability in cancer.",

keywords = "Cancer, DNA replication, Genomic instability, Oncogene, Replication stress",

author = "Dan Sarni and Batsheva Kerem",

note = "Funding Information: This work was partially supported by grants from the Israel Science Foundation (Grant No. 176/11), Israel Science Foundation (Grant No. 2535/16), The Chief Scientist Office of the Israel Ministry of Health (Grant No. 3-00000-6014), the Israeli Cancer Association (grant No. 20141044), the Israeli centers of research excellence (I-CORE), Gene Regulation in Complex Human Disease, Center Number 41/11, and by the Cooperation Program in Cancer Research of the Deutsches Krebsforschungszentrum (DKFZ) and Israel{\textquoteright}s Ministry of Science and Technology (MOST). We thank all members of the Kerem lab for thoughtful discussions Publisher Copyright: {\textcopyright} 2017 by the authors. Licensee MDPI, Basel, Switzerland.",

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N1 - Funding Information: This work was partially supported by grants from the Israel Science Foundation (Grant No. 176/11), Israel Science Foundation (Grant No. 2535/16), The Chief Scientist Office of the Israel Ministry of Health (Grant No. 3-00000-6014), the Israeli Cancer Association (grant No. 20141044), the Israeli centers of research excellence (I-CORE), Gene Regulation in Complex Human Disease, Center Number 41/11, and by the Cooperation Program in Cancer Research of the Deutsches Krebsforschungszentrum (DKFZ) and Israel’s Ministry of Science and Technology (MOST). We thank all members of the Kerem lab for thoughtful discussions Publisher Copyright: © 2017 by the authors. Licensee MDPI, Basel, Switzerland.

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N2 - Genomic instability plays a key role in driving cancer development. It is already found in precancerous lesions and allows the acquisition of additional cancerous features. A major source of genomic instability in early stages of tumorigenesis is DNA replication stress. Normally, origin licensing and activation, as well as replication fork progression, are tightly regulated to allow faithful duplication of the genome. Aberrant origin usage and/or perturbed replication fork progression leads to DNA damage and genomic instability. Oncogene activation is an endogenous source of replication stress, disrupting replication regulation and inducing DNA damage. Oncogene-induced replication stress and its role in cancer development have been studied comprehensively, however its molecular basis is still unclear. Here, we review the current understanding of replication regulation, its potential disruption and how oncogenes perturb the replication and induce DNA damage leading to genomic instability in cancer.

AB - Genomic instability plays a key role in driving cancer development. It is already found in precancerous lesions and allows the acquisition of additional cancerous features. A major source of genomic instability in early stages of tumorigenesis is DNA replication stress. Normally, origin licensing and activation, as well as replication fork progression, are tightly regulated to allow faithful duplication of the genome. Aberrant origin usage and/or perturbed replication fork progression leads to DNA damage and genomic instability. Oncogene activation is an endogenous source of replication stress, disrupting replication regulation and inducing DNA damage. Oncogene-induced replication stress and its role in cancer development have been studied comprehensively, however its molecular basis is still unclear. Here, we review the current understanding of replication regulation, its potential disruption and how oncogenes perturb the replication and induce DNA damage leading to genomic instability in cancer.

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KW - DNA replication

KW - Genomic instability

KW - Oncogene

KW - Replication stress

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DO - 10.3390/ijms18071339

M3 - Review article

AN - SCOPUS:85021425541

SN - 1661-6596

VL - 18

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JF - International Journal of Molecular Sciences

IS - 7

M1 - 1339

ER -

Oncogene-induced replication stress drives genome instability and tumorigenesis

Abstract

Bibliographical note

Keywords

UN SDGs

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