The DNA sequence specificity of bleomycin cleavage in a systematically altered DNA sequence

作者：Gautam Shweta D; Chen Jon K; Murray Vincent^*

来源：Journal of Biological Inorganic Chemistry, 2017, 22(6): 881-892.

DOI：10.1007/s00775-017-1466-z

• Bleomycin
• Cleavage sites
• DNA damage
• DNA sequence specificity
• Consensus sequence
• Plasmid vs genome-wide

Bleomycin is an anti-tumour agent that is clinically used to treat several types of cancers. Bleomycin cleaves DNA at specific DNA sequences and recent genome-wide DNA sequencing specificity data indicated that the sequence 5'-RTGT*AY (where T* is the site of bleomycin cleavage, R is G/A and Y is T/C) is preferentially cleaved by bleomycin in human cells. Based on this DNA sequence, we constructed a plasmid clone to explore this bleomycin cleavage preference. By systematic variation of single nucleotides in the 5'-RTGT*AY sequence, we were able to investigate the effect of nucleotide changes on bleomycin cleavage efficiency. We observed that the preferred consensus DNA sequence for bleomycin cleavage in the plasmid clone was 5'-YYGT*AW (where W is A/T). The most highly cleaved sequence was 5'-TCGT*AT and, in fact, the seven most highly cleaved sequences conformed to the consensus sequence 5'-YYGT*AW. A comparison with genome-wide results was also performed and while the core sequence was similar in both environments, the surrounding nucleotides were different.

• 出版日期2017-8