GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE318nnn/GSE318306/primaryOK200TranscriptomicsHomo sapiens Non-coding RNA profiling by high throughput sequencingExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE318306GEOGSEfalseWhole transcriptome sequencing of HCT116 cells with altered DNA repair capacities treated with RTX or 5FdURThymidylate synthase (TS) is a key enzyme in thymidylate biosynthesis and an established target of chemotherapeutics such as 5-fluoro-2’-deoxyuridine (5FdUR) and raltitrexed (RTX). Inhibition of TS disrupts the dUTP:dTTP balance, leading to uracil misincorporation, futile base excision repair cycles, DNA strand breaks, and ultimately cell death. However, active U-DNA repair is apparently not required for the cytotoxic effect of these drugs, indicating that alternative pathways contribute to the observed S-phase arrest. To dissect these mechanisms, we investigated the transcriptomic effects of TS inhibition in HCT116 colon cancer cell lines with altered DNA repair capacities treated with 5-fluoro-2′-deoxyuridine (5FdUR) or raltitrexed (RTX). Both drugs induced similar DNA damage responses and S-phase arrest, yet displayed distinct transcriptional signatures. Our findings underscore the multifaceted impact of TS inhibition and reveal drug-specific differences in cellular responses.2026/07/08GSE318306GSM9492049GSM9492050GSM9492072GSM9492051GSM9492073GSM9492070GSM9492071GSM9492054GSM9492076GSM9492055GSM9492052GSM9492074GSM9492075GSM9492053GSM9492058GSM9492059GSM9492056GSM9492057GSM9492061GSM9492062GSM9492060GSM9492043GSM9492065GSM9492044GSM9492066GSM9492041GSM9492063GSM9492064GSM9492042GSM9492047GSM9492069GSM9492048GSM9492067GSM9492045GSM9492046GSM949206824676318306Homo sapiens[42384741]