Consistently with our observations, Weeks et al recently showed that treatment with the antifolate pemetrexed in UNG -/- human colon cancer cells led to preferential enrichment of double-strand breaks (DSBs) within highly accessible euchromatic regions, like transcription factor binding sites, origins of replication, DNase hypersensitivity regions and CpG islands (Weeks et al., 2014). The gene discussed is UNG; the disease is malignant colon neoplasm.