title: Common Chemical Inductors of Replication Stress:  Focus on Cell-Based Studies.
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.
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Hnevotinska 5, Olomouc 779 00, Czech Republic. eva.vesela@upol.cz.|MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK. eva.vesela@upol.cz.
authors.forename: Eva
authors.initials: E
authors.lastname: Vesela
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Hnevotinska 5, Olomouc 779 00, Czech Republic. katarina.chroma@upol.cz.
authors.forename: Katarina
authors.initials: K
authors.lastname: Chroma
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Hnevotinska 5, Olomouc 779 00, Czech Republic. zsofia.turi01@upol.cz.
authors.forename: Zsofia
authors.initials: Z
authors.lastname: Turi
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Hnevotinska 5, Olomouc 779 00, Czech Republic. martin.mistrik@upol.cz.
authors.forename: Martin
authors.initials: M
authors.lastname: Mistrik
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D002477:Cells / Q000187:drug effects / Q000378:metabolism*; D004261:DNA Replication / Q000187:drug effects; D006801:Humans; D013312:Stress, Physiological / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents
keywords: replication stress;  aphidicolin;  camptothecin;  cancer;  cisplatin;  etoposide;  hydroxyurea