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非同源DNA末端连接中重叠形成的机制。

Mechanisms of overlap formation in nonhomologous DNA end joining.

作者信息

Pfeiffer P, Thode S, Hancke J, Vielmetter W

机构信息

Institut für Genetik, Universität zu Köln, Federal Republic of Germany.

出版信息

Mol Cell Biol. 1994 Feb;14(2):888-95. doi: 10.1128/mcb.14.2.888-895.1994.

DOI:10.1128/mcb.14.2.888-895.1994
PMID:8289828
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC358443/
Abstract

Rejoining of nonhomologous DNA termini plays a central role in processes of illegitimate recombination. In Xenopus egg extracts, DNA ends with noncomplementary 4-nucleotide antiparallel single-strand protrusions are assumed to be joined by formation of short mismatched overlap intermediates. The extents of these overlaps may be set by single fortuitously matching base pairs and determine the patterns of subsequent gap filling and nick ligation. Under conditions of alternative overlap settings, rules for the most probable joining pathway and the effects of mismatches on junction formation were analyzed. We show that in certain cases, fill-in and ligation converting overlap intermediates into covalently closed junctions may proceed in the presence of unrepaired mismatches, whereas in other cases, completion of junction formation is preceded by removal of mismatches. Results are discussed in relation with "alignment" proteins postulated to structurally support overlap heteroduplexes during junction formation.

摘要

非同源DNA末端的重新连接在异常重组过程中起着核心作用。在非洲爪蟾卵提取物中,具有非互补4核苷酸反平行单链突出端的DNA末端被认为是通过形成短的错配重叠中间体而连接的。这些重叠的程度可能由单个偶然匹配的碱基对决定,并决定随后的缺口填补和切口连接模式。在交替重叠设置的条件下,分析了最可能的连接途径规则以及错配对连接形成的影响。我们表明,在某些情况下,将重叠中间体转化为共价闭合连接的填补和连接可能在未修复错配的情况下进行,而在其他情况下,连接形成的完成之前会去除错配。结合假定在连接形成过程中在结构上支持重叠异源双链体的“比对”蛋白对结果进行了讨论。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dac/358443/fb0e39d10d70/molcellb00002-0034-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dac/358443/fb0e39d10d70/molcellb00002-0034-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dac/358443/fb0e39d10d70/molcellb00002-0034-a.jpg

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Base damage immediately upstream from double-strand break ends is a more severe impediment to nonhomologous end joining than blocked 3'-termini.双链断裂末端上游的基本损伤比对 3’端受阻更严重地阻碍非同源末端连接。
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