Vanillins--a novel family of DNA-PK inhibitors.

ABSTRACT: Non-homologous DNA end-joining (NHEJ) is a major pathway of double strand break (DSB) repair in human cells. Here we show that vanillin (3-methoxy-4-hydroxybenzaldehyde)--a naturally occurring food component and an acknowledged antimutagen, anticlastogen and anticarcinogen--is an inhibitor of NHEJ. Vanillin blocked DNA end-joining by human cell extracts by directly inhibiting the activity of DNA-PK, a crucial NHEJ component. Inhibition was selective and vanillin had no detectable effect on other steps of the NHEJ process, on an unrelated protein kinase or on DNA mismatch repair by cell extracts. Subtoxic concentrations of vanillin did not affect the ATM/ATR-dependent phosphorylation of Chk2 or the S-phase checkpoint response after ionising radiation. They significantly potentiated the cyto

SUBMITTER: Durant S 

PROVIDER: S-EPMC206453 | biostudies-literature | 2003 Oct

REPOSITORIES: biostudies-literature