Genome-wide mapping of the DNA modification uracil and its mechanism of incorporation into DNA
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The incorporation and creation of modified nucleobases in DNA have profound effects on genome function. In this study, we developed a novel, specific method for mapping positions and local content of modified DNA nucleobases through combination of in vitro base excision with massively parallel DNA sequencing. We applied this method, named Excision-seq, to map uracil in Escherichia coli and Saccharomyces cerevisiae, and discovered significant variation in uracil content wherein uracil is excluded from the earliest and latest-replicating regions of the genome. Widely used antimetabolite chemotherapies ...