Interplay between Cellular Metabolism and the DNA Damage Response in Cancer

Abstract

Metabolism is a fundamental cellular process that can become harmful for cells by leading to DNA damage, for instance by an increase in oxidative stress or through the generation of toxic byproducts. To deal with such insults, cells have evolved sophisticated DNA damage response (DDR) pathways that allow for the maintenance of genome integrity. Recent years have seen remarkable progress in our understanding of the diverse DDR mechanisms, and, through such work, it has emerged that cellular metabolic regulation not only generates DNA damage but also impacts on DNA repair. Cancer cells show an alteration of the DDR coupled with modifications in cellular metabolism, further emphasizing links between these two fundamental processes. Taken together, these compelling findings indicate that metabolic enzymes and metabolites represent a key group of factors within the DDR. Here, we will compile the current knowledge on the dynamic interplay between metabolic factors and the DDR, with a specific focus on cancer. We will also discuss how recently developed high-throughput technologies allow for the identification of novel crosstalk between the DDR and metabolism, which is of crucial importance to better design efficient cancer treatments.

cGAS/STING: novel perspectives of the classic pathway

“…As we discussed above, the formation of micronuclei is an important mark of genomic instability. And genomic instability caused by the activation of multipolar mitotic spindles [50], the production of DNA-damage agents [51], centrosome abnormalities [52], telomeres dysfunctions [53][54][55] andp53/p21 mutation [56] are hallmarks of cancer and cellular senescence. The disruption of the micronuclei caused by aberrant accumulation of the endosomal sorting complex required for transport-III (ESCRT-III) complex or the mutant prelamin A (progerin) accentuates DNA damage and enhances proinflammatory responses via cGAS/STING pathway [57][58][59].…”

Toward a Consensus in the Repertoire of Hemocytes Identified in Drosophila

“…Maf-S along with Foxo regulate oxidative stress resistance ( Rahman et al, 2013 ; Gumeni et al, 2019 ) and CHES-1-like is involved in the DNA-damage response ( Busygina et al, 2006 ). Both oxidative stress and DNA damage can be associated with the high metabolism of lamellocytes, a phenomenon usually observed in cancerous cells in mammals ( Moretton and Loizou, 2020 ).…”

Metabolite Reanalysis Revealed Potential Biomarkers for COVID-19: A Potential Link with Immune Response

“…There was a significant increase in cytosine and ribose, indicated by the overrepresentation of purine ribonucleotides degradation. The upregulations of purine nucleotides degradation II (aerobic) and other nucleic acid metabolome pathways were indicators of inflammation [ 30 ]. On the other hand, β-alanine, tauroursodeoxycholic and taurocholic acid were also elevated in COVID-19 patients, which have been suggested to be involved in the negative feedback of the inflammation that plays a certain role in immune regulation [ 31–33 ].…”