Cleavage of a model DNA replication fork by a methyl-specific endonuclease.
Cleavage of a model DNA replication fork by a methyl-specific endonuclease.
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DOI：
10.1093/nar/gkr153
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发表时间：
2011-07
影响因子：
14.9
通讯作者：
Kobayashi I
中科院分区：
文献类型：
--
作者：
Ishikawa K;Handa N;Sears L;Raleigh EA;Kobayashi I
表观遗传DNA甲基化参与许多生物学过程。表观遗传状态可以通过DNA甲基转移酶基因或其活性的获得或丧失而改变。DNA损伤的修复也可以去除DNA甲基化。响应于这样的改变，检测DNA甲基化的DNA内切核酸酶可以起作用并且可能导致细胞死亡。在这里，我们探讨了大肠杆菌的甲基化依赖性DNA酶McrBC在复制叉处切割DNA的可能性。首先，我们发现在没有同源重组的情况下，McrBC对携带外源DNA甲基转移酶基因的噬菌体的体内限制增加。这表明某些切割事件通过重组修复，并且必须在复制期间或之后发生。接下来，我们证明了该酶可以在体外切割模型DNA复制叉。分叉的切割需要在两个臂上进行甲基化，并且移除一个、另一个或两个臂。大多数切割事件从叉上去除甲基化位点。这一结果表明，即使很少发生的修饰模式的收购将被识别和拒绝有效的修饰依赖性限制系统，识别两个网站。这一过程可能有助于通过程序性细胞死亡保持基因组沿着的表观遗传状态。
Epigenetic DNA methylation is involved in many biological processes. An epigenetic status can be altered by gain or loss of a DNA methyltransferase gene or its activity. Repair of DNA damage can also remove DNA methylation. In response to such alterations, DNA endonucleases that sense DNA methylation can act and may cause cell death. Here, we explored the possibility that McrBC, a methylation-dependent DNase of Escherichia coli, cleaves DNA at a replication fork. First, we found that in vivo restriction by McrBC of bacteriophage carrying a foreign DNA methyltransferase gene is increased in the absence of homologous recombination. This suggests that some cleavage events are repaired by recombination and must take place during or after replication. Next, we demonstrated that the enzyme can cleave a model DNA replication fork in vitro. Cleavage of a fork required methylation on both arms and removed one, the other or both of the arms. Most cleavage events removed the methylated sites from the fork. This result suggests that acquisition of even rarely occurring modification patterns will be recognized and rejected efficiently by modification-dependent restriction systems that recognize two sites. This process might serve to maintain an epigenetic status along the genome through programmed cell death.
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影响因子：
12.3
作者：
Fukuda, Eri;Kaminska, Katarzyna H.;Bujnicki, Janusz M.;Kobayashi, Ichizo
通讯作者：
Kobayashi, Ichizo
影响因子：
14.9
作者：
Ishikawa, Ken;Handa, Naofumi;Kobayashi, Ichizo
通讯作者：
Kobayashi, Ichizo
影响因子：
3.2
作者：
Anton, BP;Raleigh, EA
通讯作者：
Raleigh, EA
影响因子：
2.1
作者：
Handa, N;Ohashi, S;Kobayashi, I
通讯作者：
Kobayashi, I
影响因子：
3.7
作者：
Gast, FU;Brinkmann, T;Pingoud, A
通讯作者：
Pingoud, A