Suppressing PARylation by 2'-5'-oligoadenylate synthetase 1 inhibits DNA damage-induced cell death

ABSTRACT: High expression of 2',5'-oligoadenylate synthetase 1 (OAS1), which adds AMP residues in 2', 5' linkage to a variety of substrates, is observed in many cancers as a part of the Interferon-Related DNA Damage Resistance Signature (IRDS). Poly(ADP-ribose) (PAR) is rapidly synthesized from NAD+ at sites of DNA damage to facilitate repair, but excessive PAR synthesis due to extensive DNA damage results in cell death by energy depletion and/or activation of PAR-dependent programmed cell death pathways. We find that OAS1 adds AMP residues in 2'-5' linkage to PAR, inhibiting its synthesis in vitro and reducing its accumulation in cells. Increased OAS1 expression substantially improves cell viability following DNA-damaging treatments that stimulate PAR synthesis during DNA repair. We conclude that h

SUBMITTER: Dr. Anna, A Kondratova 

PROVIDER: S-SCDT-EMBOJ-2019-101573 | biostudies-other |

REPOSITORIES: biostudies-other