Hairpin DNA sequences bound strongly by bleomycin exhibit enhanced double-strand cleavage.
Hairpin DNA sequences bound strongly by bleomycin exhibit enhanced double-strand cleavage.
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DOI：
10.1021/ja500414a
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发表时间：
2014-03-19
影响因子：
15
通讯作者：
Hecht, Sidney M.
中科院分区：
文献类型：
--
作者：
Roy, Basab;Hecht, Sidney M.
临床上使用的博莱霉素 A5 已用于对 10 个发夹 DNA 文库进行双链切割的研究，该文库最初是根据与博来霉素的强结合而选择的。每一种 DNA 都在多个位点经历双链切割，并且所有切割位点都位于双链体的八个碱基对区域内或附近，该区域已被随机化以创建原始文库。在这 10 个 DNA 上总共鉴定了 31 个双链切割位点，其中 14 个位点被发现代表偶联切割位点，即两条链中的一条总是先被切割，然后是相对链上的相关位点的事件。这些偶联位点中的大多数都通过 Povirk 实验室先前描述的机制进行了裂解，并提供了与报道的完全相似的裂解模式。然而，注意到至少一个偶联裂解事件不符合先前描述的模式。更令人惊讶的是，发现 17 个双链裂解不是由偶联双链裂解引起的，并且我们假设这些裂解是由以前未描述过的新机制引起的。这些位点增强的双链裂解似乎是 Fe·BLMA5 与牢固结合的发夹 DNA 相互作用的动态性质的结果。
Clinically used bleomycin A5 has been employed in a study of double-strand cleavage of a library of 10 hairpin DNAs originally selected on the basis of their strong binding to bleomycin. Each of the DNAs underwent double-strand cleavage at more than one site, and all of the cleavage sites were within, or in close proximity to, an eight-base-pair region of the duplex that had been randomized to create the original library. A total of 31 double-strand cleavage sites were identified on the 10 DNAs, and 14 of these sites were found to represent coupled cleavage sites, that is, events in which one of the two strands was always cleaved first, followed by the associated site on the opposite strand. Most of these coupled sites underwent cleavage by a mechanism described previously by the Povirk laboratory and afforded cleavage patterns entirely analogous to those reported. However, at least one coupled cleavage event was noted that did not conform to the pattern of those described previously. More surprisingly, 17 double-strand cleavages were found not to result from coupled double-strand cleavage, and we posit that these cleavages resulted from a new mechanism not previously described. Enhanced double-strand cleavages at these sites appear to be a consequence of the dynamic nature of the interaction of Fe·BLM A5 with the strongly bound hairpin DNAs.
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DOI：
10.1073/pnas.87.21.8350
发表时间：
1990-11-01
影响因子：
11.1
作者：
STEIGHNER, RJ;POVIRK, LF
通讯作者：
POVIRK, LF
影响因子：
2.9
作者：
ABSALON, MJ;WU, W;STUBBE, J
通讯作者：
STUBBE, J
影响因子：
4.1
作者：
Charles, K;Povirk, LF
通讯作者：
Povirk, LF
影响因子：
2.9
作者：
MURUGESAN, N;XU, C;HECHT, SM
通讯作者：
HECHT, SM
影响因子：
15
作者：
Akiyama, Yoshitsugu;Ma, Qian;Hecht, Sidney M.
通讯作者：
Hecht, Sidney M.