Cell death upon epigenetic genome methylation: a novel function of methyl-specific deoxyribonucleases.

Cell death upon epigenetic genome methylation: a novel function of methyl-specific deoxyribonucleases.
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DOI:
10.1186/gb-2008-9-11-r163
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发表时间:
2008
期刊:
影响因子:
12.3
通讯作者:
Kobayashi, Ichizo
Kobayashi, Ichizo
中科院分区:
生物学1区
文献类型:
--
作者:
Fukuda, Eri;Kaminska, Katarzyna H.;Bujnicki, Janusz M.;Kobayashi, Ichizo

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来自大肠杆菌的McrBC甲基特异性脱氧核糖核酸酶可以通过杀死宿主来响应基因组甲基化。表观遗传甲基化的改变可以影响基因表达和其他过程。在原核生物中,DNA甲基转移酶基因经常在基因组之间移动,并构成潜在威胁。大肠杆菌的一种甲基特异性脱氧核糖核酸酶McrBC可以切割入侵的甲基化DNA。在这里,我们研究了McrBC是否通过染色体切割杀死宿主而与基因组甲基化系统竞争。McrBC抑制了携带PvuII甲基转移酶基因但缺乏其识别位点的质粒的建立,可能是通过甲基化的染色体的致死性切割。事实上,其噬菌体介导的转移引起McrBC依赖性染色体切割。它的诱导导致细胞死亡,伴随着染色体甲基化,分裂和降解。RecA/RecBCD功能影响染色体加工,并与SOS反应一起降低致死率。我们的进化/基因组分析McrBC同源物显示:广泛分布在原核生物;频繁的远距离水平转移和与流动性相关的基因连锁;和多样化的DNA结合域。在这些特征中,McrBC类似于II型限制修饰系统,其表现为自私的移动的元件,通过宿主杀伤来维持其频率。McrBC经常被发现与甲基转移酶同源物连接,这表明了功能关联。我们的实验表明McrBC可以通过宿主杀伤来响应基因组甲基化系统。结合我们的进化/基因组分析,它们支持我们的假设,即McrBC已经进化为通过宿主杀伤与特定基因组甲基化系统竞争的移动的元件。据我们所知,这是第一次报告的防御系统对表观遗传系统通过细胞死亡。
The McrBC methyl-specific deoxyribonuclease from Escherichia coli can respond to genome methylation by host killing. Alteration in epigenetic methylation can affect gene expression and other processes. In Prokaryota, DNA methyltransferase genes frequently move between genomes and present a potential threat. A methyl-specific deoxyribonuclease, McrBC, of Escherichia coli cuts invading methylated DNAs. Here we examined whether McrBC competes with genome methylation systems through host killing by chromosome cleavage. McrBC inhibited the establishment of a plasmid carrying a PvuII methyltransferase gene but lacking its recognition sites, likely through the lethal cleavage of chromosomes that became methylated. Indeed, its phage-mediated transfer caused McrBC-dependent chromosome cleavage. Its induction led to cell death accompanied by chromosome methylation, cleavage and degradation. RecA/RecBCD functions affect chromosome processing and, together with the SOS response, reduce lethality. Our evolutionary/genomic analyses of McrBC homologs revealed: a wide distribution in Prokaryota; frequent distant horizontal transfer and linkage with mobility-related genes; and diversification in the DNA binding domain. In these features, McrBCs resemble type II restriction-modification systems, which behave as selfish mobile elements, maintaining their frequency by host killing. McrBCs are frequently found linked with a methyltransferase homolog, which suggests a functional association. Our experiments indicate McrBC can respond to genome methylation systems by host killing. Combined with our evolutionary/genomic analyses, they support our hypothesis that McrBCs have evolved as mobile elements competing with specific genome methylation systems through host killing. To our knowledge, this represents the first report of a defense system against epigenetic systems through cell death.
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期刊: GENE
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作者:
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期刊: BIOCHIMICA ET BIOPHYSICA ACTA
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