Compounds causing DNA damage have been used widely in molecular biology
and some are used as therapeutic agents in cancer therapy. In most cases, their cellular response
is pleiotropic, making it challenging to develop these agents efficiently for potential
therapeutic use. Furthermore, this means that such compounds can also affect healthy tissues,
which is a major drawback for the use in therapy. Thus, dissecting and understanding not only
their molecular mode of action, but also identifying all their cellular targets is critical. With
the advent of high throughput DNA sequencing technologies our understanding of the genomic
targets of such compounds has increased significantly over recent years. This review
gives an overview of some well-studied DNA-damaging agents and dissects what is known
about their molecular mode of action, their cellular response and use in clinical settings. It
then describes how high throughput-sequencing approaches can be used (a) to study DNAdamaging
compounds and (b) to gain insight into their biological activity in vivo.
Keywords: DNA damage, DDR, chemical biology, sequencing, next generation sequencing, small molecule, drug.
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