Rad54 dissociates homologous recombination intermediates by branch migration
Rad54 dissociates homologous recombination intermediates by branch migration
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DOI：
10.1038/nsmb1268
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发表时间：
2007-08-01
影响因子：
16.8
通讯作者：
Mazin, Alexander V.
中科院分区：
文献类型：
--
作者：
Bugreev, Dmitry V.;Hanaoka, Fumio;Mazin, Alexander V.
双链DNA断裂（DSB）导致细胞死亡和基因组不稳定。同源重组是一种主要的DSB修复途径，其通过与同源DNA序列形成接合分子来操作，所述接合分子用作模板以实现精确修复。在真核生物中，Rad 51蛋白（RecA同源物）搜索同源序列并催化连接分子（D-环）的形成。一旦连接分子形成，DNA聚合酶延伸断裂染色体的3'单链DNA尾，恢复丢失的信息。关节分子随后如何解离尚不清楚。我们使用纯化的人同源重组蛋白和DNA聚合酶G在体外重建DSB修复。我们发现，Rad 54蛋白，由于其ATP依赖性的分支迁移活动，可以引起关节分子的解离。这些结果表明一个以前未表征的机制DSB修复中，Rad 54分支迁移活动起着重要的作用。
Double-strand DNA breaks (DSBs) cause cell death and genome instability. Homologous recombination is a major DSB repair pathway that operates by forming joint molecules with homologous DNA sequences, which are used as templates to achieve accurate repair. In eukaryotes, Rad51 protein ( RecA homolog) searches for homologous sequences and catalyzes the formation of joint molecules (D-loops). Once joint molecules have been formed, DNA polymerase extends the 3' single-stranded DNA tails of the broken chromosome, restoring the lost information. How joint molecules subsequently dissociate is unknown. We reconstituted DSB repair in vitro using purified human homologous recombination proteins and DNA polymerase g. We found that Rad54 protein, owing to its ATP-dependent branch-migration activity, can cause dissociation of joint molecules. These results suggest a previously uncharacterized mechanism of DSB repair in which Rad54 branch-migration activity plays an important role.