A mechanism for deletion formation in DNA by human cell extracts: the involvement of short sequence repeats.
A mechanism for deletion formation in DNA by human cell extracts: the involvement of short sequence repeats.
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DOI：
10.1093/nar/20.23.6183
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发表时间：
1992-12
影响因子：
14.9
通讯作者：
John Thacker;Jeremy Chalk;Anil Ganesh;Phillip North
中科院分区：
文献类型：
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作者：
John Thacker;Jeremy Chalk;Anil Ganesh;Phillip North
携带位点特异性双链断裂的DNA分子暴露于来自人类细胞系的核提取物。以前的研究表明，断裂可以通过人类提取物正确地重新连接，但是一部分重新连接的分子遭受了缺失和插入。与正常细胞提取物相比，共济失调-毛细血管扩张症患者的细胞提取物的“错接”比例更高。我们现在通过序列分析表明，提取物处理的分子中的缺失仅发生在短的直接重复序列（2-6个碱基对）之间。含有300 bp插入的错误重新连接的分子在同一位点也具有基于重复的缺失。涉及许多不同的直接重复序列;然而，这些重复序列的一些聚类尤其发生在初始断点的上游侧。这些数据是最简单的解释，涉及单链暴露和修复的缺失形成的模型，也许与其他DNA代谢酶的作用影响的频率，其中一些重复。
DNA molecules carrying a site-specific double-strand break were exposed to nuclear extracts from human cell lines. It was shown previously that breaks could be rejoined correctly by human extracts, but that a proportion of the rejoined molecules had suffered deletions and insertions. The 'mis-rejoined' proportion was higher with cell extracts from an individual with the disorder ataxia-telangiectasia than with normal cell extracts. We now show by sequence analysis that deletions in extract-treated molecules occur exclusively between short direct repeats (2-6 base pairs). A mis-rejoined molecule containing an insertion of 300 bp also had a repeat-based deletion at the same site. A number of different direct repeats are involved; however, some clustering of these occurs especially on the upstream side of the initial breakpoint. These data are most simply interpreted in terms of a model of deletion formation involving single-strand exposure and repair, perhaps with the action of other DNA-metabolising enzymes influencing the frequency with which some repeats are involved.