RAD18- and BRCA1-dependent pathways promote cellular tolerance to the nucleoside analog ganciclovir.

ABSTRACT: Ganciclovir (GCV) is a clinically important drug as it is used to treat viral infections. GCV is incorporated into the DNA during replication, where it interferes with subsequent replication on GCV-incorporated templates. However, the effects of GCV on the host genome and the mechanisms underlying cellular tolerance to GCV remain unclear. In this study, we explored these mechanisms using a collection of mutant DT40 cells. We identified RAD17^/-, BRCA1^-/-, and RAD18^-/- cells as highly GCV-sensitive. RAD17, a component of the alternative checkpoint-clamp loader RAD17-RFC, was required for the activation of the intra-S checkpoint following GCV treatment. BRCA1, a critical factor for promoting homologous recombination (HR), was required for suppressing DNA doubl

SUBMITTER: Ahmad T 

PROVIDER: S-EPMC11555630 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature