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Interplay between Cellular Metabolism and the DNA Damage Response in Cancer
Amandine Moretton1,2, Joanna I Loizou1,2
1CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
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.
Insights
Cellular metabolism can cause DNA damage, but cells have DNA damage response (DDR) pathways to protect themselves. Understanding the interplay between metabolism and DDR is key for developing new cancer treatments.
Area of Science:
- Molecular Biology
- Biochemistry
- Oncology
Background:
- Cellular metabolism can lead to DNA damage through oxidative stress and toxic byproducts.
- Cells possess sophisticated DNA damage response (DDR) pathways to maintain genome integrity.
- Cancer cells exhibit altered DDR and metabolic changes, highlighting a critical link between these processes.
Purpose of the Study:
- To review the current understanding of the interplay between metabolic factors and DDR.
- To focus on the role of this interplay in cancer.
- To discuss how new technologies can identify novel crosstalk for improved cancer therapies.
Main Methods:
- Literature review and synthesis of existing research.
- Analysis of findings from high-throughput technologies.
- Focus on studies investigating metabolic regulation and DDR mechanisms.
Main Results:
- Metabolic regulation is intrinsically linked to DNA damage generation and repair.
- Metabolic enzymes and metabolites are crucial components of the DDR.
- Cancer metabolism significantly influences DDR pathways.
Conclusions:
- The dynamic interplay between metabolism and DDR is central to genome stability, particularly in cancer.
- Identifying novel crosstalk through advanced technologies is vital for advancing cancer treatment strategies.
- Metabolic enzymes and metabolites represent promising targets for cancer therapy.
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