The flap endonuclease-1 promotes cellular tolerance to a chain-terminating nucleoside analog, alovudine, by counteracting the toxic effect of 53BP1.

ABSTRACT: Chain-terminating nucleoside analogs (CTNAs) are frequently used as antiviral and anticancer agents. CTNAs are incorporated into the end of nascent DNA during DNA synthesis and inhibit subsequent DNA polymerization, thereby restricting the proliferation of viruses and cancer cells. Alovudine, a thymidine analog, exerts chain-termination effects and is used as an antiviral drug. However, the mechanisms underlying cellular tolerance to alovudine have not been fully elucidated. Here, we show that flap endonuclease-1 (Fen1) and p53 binding protein-1 (53BP1) counteractively mitigate the chain-terminating effect of alovudine. We found that the cells deficient in Fen1 (FEN1-/-) showed stronger chain-terminating effects of alovudine with augmented DNA damage than wild-type cells, leading to their

SUBMITTER: Hosen MB 

PROVIDER: S-EPMC12270548 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature