Mitotic chromosomes are constrained by topoisomerase II-sensitive DNA entanglements.
Mitotic chromosomes are constrained by topoisomerase II-sensitive DNA entanglements.
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DOI：
10.1083/jcb.200910085
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发表时间：
2010-03-08
期刊：
影响因子：
--
通讯作者：
Marko JF
中科院分区：
文献类型：
--
作者：
Kawamura R;Pope LH;Christensen MO;Sun M;Terekhova K;Boege F;Mielke C;Andersen AH;Marko JF
染色质缠结经过特定的蛋白质介导的压缩折叠成有丝分裂染色体。我们分析了有丝分裂染色体内染色质的拓扑结构。我们发现，有丝分裂染色质是严重的自我纠缠通过拓扑异构酶（拓扑异构酶）II的实验中观察到有丝分裂染色体弹性刚度降低。单染色体松弛35%的外源性添加拓扑II的方式，取决于水解腺苷三磷酸（ATP），而一个非活性拓扑II裂解突变体没有改变染色体刚度。此外，使用I型拓扑结构的实验产生了比拓扑结构II小得多的松弛效应，表明拓扑结构II的染色体松弛是由双链DNA的解链和/或解结引起的。在进一步的实验中，染色体首先暴露于蛋白酶以部分释放染色质上的蛋白质约束，ATP单独松弛有丝分裂染色体。topo II特异性抑制剂ICRF-187阻断了这种作用，表明它是由与染色体结合的内源性topo II引起的。我们的实验表明，DNA缠结与蛋白质介导的压缩一致，将染色质折叠成有丝分裂染色体。
Chromatin entanglements undergo specific protein-mediated compaction to fold into mitotic chromosomes. We have analyzed the topological organization of chromatin inside mitotic chromosomes. We show that mitotic chromatin is heavily self-entangled through experiments in which topoisomerase (topo) II is observed to reduce mitotic chromosome elastic stiffness. Single chromosomes were relaxed by 35% by exogenously added topo II in a manner that depends on hydrolysable adenosine triphosphate (ATP), whereas an inactive topo II cleavage mutant did not change chromosome stiffness. Moreover, experiments using type I topos produced much smaller relaxation effects than topo II, indicating that chromosome relaxation by topo II is caused by decatenation and/or unknotting of double-stranded DNA. In further experiments in which chromosomes are first exposed to protease to partially release protein constraints on chromatin, ATP alone relaxes mitotic chromosomes. The topo II–specific inhibitor ICRF-187 blocks this effect, indicating that it is caused by endogenous topo II bound to the chromosome. Our experiments show that DNA entanglements act in concert with protein-mediated compaction to fold chromatin into mitotic chromosomes.
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影响因子：
14.9
作者：
Linka, Rene M;Porter, Andrew C G;Volkov, Arsen;Mielke, Christian;Boege, Fritz;Christensen, Morten O
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DOI：
10.1083/jcb.115.6.1479
发表时间：
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期刊：
The Journal of cell biology
影响因子：
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作者：
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DOI：
10.1073/pnas.032095099
发表时间：
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影响因子：
11.1
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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