E. coli SbcCD and RecA control chromosomal rearrangement induced by an interrupted palindrome.

E. coli SbcCD and RecA control chromosomal rearrangement induced by an interrupted palindrome.
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DOI:
10.1016/j.molcel.2010.06.011
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发表时间:
2010-07-09
期刊:
影响因子:
16
通讯作者:
Leach DR
Leach DR
中科院分区:
生物学1区
文献类型:
--
作者:
Darmon E;Eykelenboom JK;Lincker F;Jones LH;White M;Okely E;Blackwood JK;Leach DR

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存活和基因组稳定性是健康细胞的关键特征。DNA回文对基因组稳定性构成威胁,并已被证明参与导致以自身为中心的反向染色体复制形成的反应。鉴于这种重排可能导致癌细胞基因组不稳定性,因此对这种重排的机制有相当大的兴趣。本研究表明,在大肠杆菌染色体中可以观察到大的反向染色体重复的形成。它们在不存在发夹核酸酶SbcCD和重组蛋白RecA的情况下在246 bp中断的DNA回文序列的位点处形成。这种自发重排的遗传要求与涉及DNA降解和发夹形成的途径一致,而不是十字形切割途径。因此,回文依赖的发夹中间体的形成可以通过相邻的DNA双链断裂来诱导。在E.大肠杆菌染色体SbcCD和RecA保护细胞免受反向染色体复制的影响。RecBCD降解DNA是自发反向染色体复制所必需的。发夹的形成受到回文区诱导的DNA DSB的刺激。
Survival and genome stability are critical characteristics of healthy cells. DNA palindromes pose a threat to genome stability and have been shown to participate in a reaction leading to the formation of inverted chromosome duplications centered around themselves. There is considerable interest in the mechanism of this rearrangement given its likely contribution to genome instability in cancer cells. This study shows that formation of large inverted chromosome duplications can be observed in the chromosome of Escherichia coli. They are formed at the site of a 246 bp interrupted DNA palindrome in the absence of the hairpin nuclease SbcCD and the recombination protein RecA. The genetic requirements for this spontaneous rearrangement are consistent with a pathway involving DNA degradation and hairpin formation, as opposed to a cruciform cleavage pathway. Accordingly, the formation of palindrome-dependent hairpin intermediates can be induced by an adjacent DNA double-stand break. ► Palindrome-stimulated inverted chromosome duplication occurs in E. coli chromosome ► SbcCD and RecA protect the cell against inverted chromosome duplication ► DNA degradation by RecBCD is required for spontaneous inverted chromosome duplication ► Hairpin formation is stimulated by a DNA DSB induced in the region of a palindrome
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