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Common Chemical Inductors of Replication Stress:  Focus on Cell-Based Studies.

Vesela, E; Chroma, K; Turi, Z; Mistrik, M; (2017) Common Chemical Inductors of Replication Stress:  Focus on Cell-Based Studies. Biomolecules , 7 (1) , Article 19. 10.3390/biom7010019. Green open access

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Abstract

DNA replication is a highly demanding process regarding the energy and material supply and must be precisely regulated, involving multiple cellular feedbacks. The slowing down or stalling of DNA synthesis and/or replication forks is referred to as replication stress (RS). Owing to the complexity and requirements of replication, a plethora of factors may interfere and challenge the genome stability, cell survival or affect the whole organism. This review outlines chemical compounds that are known inducers of RS and commonly used in laboratory research. These compounds act on replication by direct interaction with DNA causing DNA crosslinks and bulky lesions (cisplatin), chemical interference with the metabolism of deoxyribonucleotide triphosphates (hydroxyurea), direct inhibition of the activity of replicative DNA polymerases (aphidicolin) and interference with enzymes dealing with topological DNA stress (camptothecin, etoposide). As a variety of mechanisms can induce RS, the responses of mammalian cells also vary. Here, we review the activity and mechanism of action of these compounds based on recent knowledge, accompanied by examples of induced phenotypes, cellular readouts and commonly used doses.

Type: Article
Title: Common Chemical Inductors of Replication Stress:  Focus on Cell-Based Studies.
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/biom7010019
Publisher version: http://dx.doi.org/10.3390/biom7010019
Language: English
Additional information: © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Replication stress,  aphidicolin,  camptothecin,  cancer, cisplatin,  etoposide,  hydroxyurea
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/1544186
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