Extracellular NAD⁺ enhances PARP-dependent DNA repair capacity independently of CD73 activity.

ABSTRACT: Changes in nicotinamide adenine dinucleotide (NAD⁺) levels that compromise mitochondrial function trigger release of DNA damaging reactive oxygen species. NAD⁺ levels also affect DNA repair capacity as NAD⁺ is a substrate for PARP-enzymes (mono/poly-ADP-ribosylation) and sirtuins (deacetylation). The ecto-5'-nucleotidase CD73, an ectoenzyme highly expressed in cancer, is suggested to regulate intracellular NAD⁺ levels by processing NAD⁺ and its bio-precursor, nicotinamide mononucleotide (NMN), from tumor microenvironments, thereby enhancing tumor DNA repair capacity and chemotherapy resistance. We therefore investigated whether expression of CD73 impacts intracellular NAD⁺ content and NAD⁺-dependent DNA repair cap

SUBMITTER: Wilk A 

PROVIDER: S-EPMC6971268 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature