The DNA sequence specificity of bleomycin cleavage in a systematically altered DNA sequence
The DNA sequence specificity of bleomycin cleavage in a systematically altered DNA sequence
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DOI：
10.1007/s00775-017-1466-z
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发表时间：
2017-08-01
影响因子：
3
通讯作者：
Murray, Vincent
中科院分区：
文献类型：
--
作者：
Gautam, Shweta D.;Chen, Jon K.;Murray, Vincent
博来霉素是一种抗肿瘤药物，临床上用于治疗几种类型的癌症。博来霉素在特定的DNA序列处切割DNA，并且最近的全基因组DNA测序特异性数据表明，序列5 '-RTGT*AY（其中T* 是博来霉素切割的位点，R是G/A，Y是T/C）在人细胞中优先被博来霉素切割。基于此DNA序列，我们构建了一个质粒克隆，以探索这种博来霉素切割偏好。通过5 '-RTGT*AY序列中单个核苷酸的系统性变异，我们能够研究核苷酸变化对博来霉素切割效率的影响。我们观察到质粒克隆中博来霉素切割的优选共有DNA序列是5 ′-YYGT*AW（其中W是A/T）。最高度切割的序列是5 '-TCGT*AT，事实上，7个最高度切割的序列符合共有序列5'-YYGT*AW。还进行了与全基因组结果的比较，虽然核心序列在两种环境中相似，但周围的核苷酸不同。
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.