Topic: DNA Repair & Metabolism and Cancer Drug Resistance

Repair of DNA damage and the ensuing DNA damage response is a highly complex process that involves chromatin re-organization, the initiation of signaling networks, and cell cycle checkpoints. It mainly relies on the PARP- and SIRT-family of enzymes, across the spectrum of DNA repair and response pathways, and involves modification of DNA methylation profiles and methylation of chromatin-bound proteins. The orchestration of these protein-driven events relies on small molecule modifiers such as ATP (protein phosphorylation), NAD+ (protein ADP-ribosylation and deacylation), acyl-coA (protein acylation), and SAM (nucleic acid and histone methylation). Further, there are additional processes that engage and regulate macromolecules such as ubiquitylation, NEDDylation and SUMOylation. Crucially, each small molecule modifier is a cofactor that is consumed in such cellular processes and is directly involved in and affected by central cellular metabolic processes. Importantly, metabolism is an adaptive process often observed to be dramatically different in cancer, which is considered to be a hallmark of cancer and of cancer drug resistance. The abundance and availability of these cofactors might greatly affect DNA repair and the cellular response to cancer drug treatment. Through metabolic adaptation, be it causative or consecutive to the emergence of drug resistance, the axis between DNA repair, metabolism, and cancer drug resistance offers a scope for greater understanding of this synergy and covers the research that this Special Issue on cancer drug resistance seeks to encompass. Overall, we are looking for submissions that highlight the interconnectivity and interdependence of DNA repair and metabolism in cancer drug resistance.

15 Jun 2023