Single-nucleotide-resolution genomic maps of O6-methylguanine from the glioblastoma drug temozolomide.

ABSTRACT: Temozolomide kills cancer cells by forming O6-methylguanine (O6-MeG), which leads to cell cycle arrest and apoptosis. However, O6-MeG repair by O6-methylguanine-DNA methyltransferase (MGMT) contributes to drug resistance. Characterizing genomic profiles of O6-MeG could elucidate how O6-MeG accumulation is influenced by repair, but there are no methods to map genomic locations of O6-MeG. Here, we developed an immunoprecipitation- and polymerase-stalling-based method, termed O6-MeG-seq, to locate O6-MeG across the whole genome at single-nucleotide resolution. We analyzed O6-MeG formation and repair across sequence contexts and functional genomic regions in relation to MGMT expression in a glioblastoma-derived cell line. O6-MeG signatures were highly similar to mutational signatures from pati

SUBMITTER: Kubitschek J 

PROVIDER: S-EPMC11744188 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature