Format

Send to

Choose Destination
Biomolecules. 2017 Feb 21;7(1). pii: E19. doi: 10.3390/biom7010019.

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

Author information

1
Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Hnevotinska 5, Olomouc 779 00, Czech Republic. eva.vesela@upol.cz.
2
MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK. eva.vesela@upol.cz.
3
Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Hnevotinska 5, Olomouc 779 00, Czech Republic. katarina.chroma@upol.cz.
4
Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Hnevotinska 5, Olomouc 779 00, Czech Republic. zsofia.turi01@upol.cz.
5
Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Hnevotinska 5, Olomouc 779 00, Czech Republic. martin.mistrik@upol.cz.

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.

KEYWORDS:

replication stress;  aphidicolin;  camptothecin;  cancer;  cisplatin;  etoposide;  hydroxyurea

PMID:
28230817
PMCID:
PMC5372731
DOI:
10.3390/biom7010019
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center