Action of bleomycin on structural mimics of intermediates in DNA double-strand cleavage
Action of bleomycin on structural mimics of intermediates in DNA double-strand cleavage
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DOI：
10.1021/tx980154g
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发表时间：
1998-12-01
影响因子：
4.1
通讯作者：
Povirk, LF
中科院分区：
文献类型：
--
作者：
Charles, K;Povirk, LF
在几个切口，缺口或完整的双链体DNA中检查博来霉素诱导的切割。底物，包括设计用于模拟双链切割中提出的单切口中间体的结构。该切口结构似乎正确靶向互补链中的第二次切割事件，导致平端双链断裂，类似于在相同序列的完整双链体中单独戈伊博来霉素直接诱导的双链断裂。一个碱基缺口的结构在正确靶向博来霉素攻击互补链中的效率明显较低。结果与博来霉素诱导的双链切割模型一致，其中由初始博来霉素攻击形成的切口用于将二次攻击靶向互补链中的特定位置，导致具有限定几何形状的双链断裂。
Bleomycin-induced cleavage was examined in several nicked, gapped or intact duplex DNA. substrates, including a structure designed to mimic a proposed singly nicked intermediate in double-strand cleavage. This nicked structure appeared to correctly target the second cleavage event in the complementary strand, resulting in a blunt-ended double-strand break, similar to that Induced directly Gy bleomycin alone in an intact duplex of the same sequence. A one-base-gapped structure was markedly Less efficient in correctly targeting bleomycin attack in the complementary strand. The results are consistent with a model of bleomycin-induced double-strand cleavage in which the nick formed by the initial bleomycin attack serves to target secondary attack to a specific position in the complementary strand, resulting in a double-strand break with a defined geometry.