4.6 Review

The emerging relationship between metabolism and DNA repair

Journal

CELL CYCLE
Volume 20, Issue 10, Pages 943-959

Publisher

TAYLOR & FRANCIS INC
DOI: 10.1080/15384101.2021.1912889

Keywords

DNA repair; metabolism; mitochondria

Categories

Funding

  1. Barts Charity [MGU0478]
  2. Cancer Research UK [C16420/A18066]
  3. Medical Research Council [MR/K001620/1]

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The DNA damage response (DDR) and cellular metabolism are closely related, with metabolic pathways influencing DDR repair process and DDR proteins regulating metabolic flux. This connection holds great importance in cancer biology.
The DNA damage response (DDR) consists of multiple specialized pathways that recognize different insults sustained by DNA and repairs them where possible to avoid the accumulation of mutations. While loss of activity of genes in the DDR has been extensively associated with cancer predisposition and progression, in recent years it has become evident that there is a relationship between the DDR and cellular metabolism. The activity of the metabolic pathways can influence the DDR by regulating the availability of substrates required for the repair process and the function of its players. Additionally, proteins of the DDR can regulate the metabolic flux through the major pathways such as glycolysis, tricarboxylic acid cycle (TCA) and pentose phosphate pathway (PPP) and the production of reactive oxygen species (ROS). This newly discovered connection bears great importance in the biology of cancer and represents a new therapeutic opportunity. Here we describe the nature of the relationship between DDR and metabolism and its potential application in the treatment of cancer. Keywords: DNA repair, metabolism, mitochondria

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