Oncometabolites suppress DNA repair by disrupting local chromatin signalling.

ABSTRACT: Deregulation of metabolism and disruption of genome integrity are hallmarks of cancer¹. Increased levels of the metabolites 2-hydroxyglutarate, succinate and fumarate occur in human malignancies owing to somatic mutations in the isocitrate dehydrogenase-1 or -2 (IDH1 or IDH2) genes, or germline mutations in the fumarate hydratase (FH) and succinate dehydrogenase genes (SDHA, SDHB, SDHC and SDHD), respectively^2-4. Recent work has made an unexpected connection between these metabolites and DNA repair by showing that they suppress the pathway of homology-dependent repair (HDR)^5,6 and confer an exquisite sensitivity to inhibitors of poly (ADP-ribose) polymerase (PARP) that are being tested in clinical trials. However, the mechanism by which these oncometabolite

SUBMITTER: Sulkowski PL 

PROVIDER: S-EPMC7319896 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature