Phage Mu transposition immunity: protein pattern formation along DNA by a diffusion-ratchet mechanism.

Phage Mu transposition immunity: protein pattern formation along DNA by a diffusion-ratchet mechanism.
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DOI:
10.1016/j.molcel.2010.06.013
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发表时间:
2010-07-09
期刊:
影响因子:
16
通讯作者:
Mizuuchi K
Mizuuchi K
中科院分区:
生物学1区
文献类型:
--
作者:
Han YW;Mizuuchi K

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DNA转座子以有限的靶序列特异性整合到宿主染色体中。如果没有避免插入自身的机制,转座子就有自我毁灭的风险。噬菌体Mu通过涉及mua转座酶和MuB atp依赖的dna结合蛋白的转座免疫来避免这个问题。MuB结合的DNA是一个有效的转位靶标,但与Mu DNA末端结合的MuA簇激活MuB- atp酶,并在目标位点承诺之前将MuB从其邻近区域解离,使Mu末端附近的区域成为一个不良靶标。这种MuA簇- mub相互作用需要在MuA-和mub结合的DNA位点之间形成DNA环。在早期,MuB星团通过平均尺寸较小的环被分解,而在后期,MuA星团通过形成平均尺寸较大的环来寻找距离较远的MuB星团。我们证明了带有中间扩散步骤的迭代环形成/破坏周期导致更大的dna环,导致转座子优先插入到远离转座子末端的位置。
DNA transposons integrate into host chromosomes with limited target sequence-specificity. Without mechanisms to avoid insertion into themselves, transposons risk self-destruction. Phage Mu avoids this problem by transposition immunity, involving MuA-transposase and MuB ATP-dependent DNA-binding protein. MuB-bound DNA acts as an efficient transposition target, but MuA clusters bound to Mu DNA ends activate the MuB-ATPase and dissociate MuB from their neighborhood before target site commitment, making the regions near Mu ends a poor target. This MuA-cluster-MuB interaction requires formation of DNA loops between the MuA- and the MuB-bound DNA sites. At early times, MuB clusters are disassembled via loops with smaller average size and at later times, MuA clusters find distantly located MuB clusters by forming loops with larger average sizes. We demonstrate that iterative loop formation/disruption cycles with intervening diffusional steps result in larger DNA-loops, leading to preferential insertion of the transposon at sites distant from the transposon ends.
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