Bleomycin (BLM) is a cancer chemotherapeutic agent that cleaves cellular DNA at specific sequences. Using next-generation Illumina sequencing, the genome-wide sequence specificity of DNA cleavage by two BLM analogues, 6′-deoxy-BLM Z and zorbamycin (ZBM), was determined in human HeLa cells and compared with BLM. Over 200 million double-strand breaks were examined for each sample, and the 50,000 highest intensity cleavage sites were analysed. It was found that the DNA sequence specificity of the BLM analogues in human cells was different to BLM, especially at the cleavage site (position “0”) and the “+1” position. In human cells, the 6′-deoxy-BLM Z had a preference for 5′-GTGY*MC (where * is the cleavage site, Y is C or T, M is A or C); it was 5′-GTGY*MCA for ZBM; and 5′-GTGT*AC for BLM. With cellular DNA, the highest ranked tetranucleotides were 5′-TGC*C and 5′-TGT*A for 6′-deoxy-BLM Z; 5′-TGC*C, 5′-TGT*A and 5′-TGC*A for ZBM; and 5′-TGT*A for BLM. In purified human genomic DNA, the DNA sequence preference was 5′-TGT*A for 6′-deoxy-BLM, 5′-RTGY*AYR (where R is G or A) for ZBM, and 5′-TGT*A for BLM. Thus, the sequence specificity of the BLM analogue, 6′-deoxy-BLM Z, was similar to BLM in purified human DNA, while ZBM was different.

博来霉素（BLM）是一种癌症化学治疗剂，可按特定序列切割细胞DNA。使用下一代Illumina测序，确定了人类HeLa细胞中两个BLM类似物6'-脱氧-BLM Z和佐巴霉素（ZBM）切割DNA的全基因组序列特异性，并将其与BLM进行了比较。每个样品检查了超过2亿条双链断裂，并分析了50,000个最高强度的切割位点。发现人细胞中BLM类似物的DNA序列特异性不同于BLM，特别是在切割位点（“ 0”位）和“ +1”位。在人细胞中，6'-脱氧-BLM Z具有5'-GTGY * MC的优先权（其中*为切割位点，Y为C或T，M为A或C）；ZBM是5′-GTGY * MCA；和5'-GTGT * AC用于BLM。有了细胞DNA，对于6'-脱氧-BLM Z，排名最高的四核苷酸为5'-TGC * C和5'-TGT * A；ZBM的5'-TGC * C，5'-TGT * A和5'-TGC * A; 以及BLM的5'-TGT * A。在纯化的人类基因组DNA中，对于6'-脱氧-BLM，DNA序列优先级为5'-TGT * A，对于ZBM为5'-RTGY * AYR（其中R为G或A），对于5'-TGT * A为DNA BLM。因此，在纯化的人DNA中，BLM类似物6'-脱氧-BLM Z的序列特异性类似于BLM，而ZBM则不同。