The DNA helicase Large helicase-related (Lhr) is present throughout archaea, including in the Asgard and Nanoarchaea, and has homologues in bacteria and eukaryotes. It is thought to function in DNA repair but in a context that is not known. Our data show that archaeal Lhr preferentially targets DNA replication fork structures. In a genetic assay, expression of archaeal Lhr gave a phenotype identical to the replication-coupled DNA repair enzymes Hel308 and RecQ. Purified archaeal Lhr preferentially unwound model forked DNA substrates compared with DNA duplexes, flaps and Holliday junctions, and unwound them with directionality. Single-molecule FRET measurements showed that binding of Lhr to a DNA fork causes ATP-independent distortion and base-pair melting at, or close to, the fork branchpoint. ATP-dependent directional translocation of Lhr resulted in fork DNA unwinding through the ‘parental’ DNA strands. Interaction of Lhr with replication forks in vivo and in vitro suggests that it contributes to DNA repair at stalled or broken DNA replication.

中文翻译：

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关于Lhr解旋酶在DNA修复中的作用机理的见解。

DNA解旋酶大型解旋酶相关（Lhr）存在于整个古细菌中，包括在Asgard和Nanoarchaea中，并且在细菌和真核生物中具有同系物。人们认为它在DNA修复中起作用，但是在未知的情况下起作用。我们的数据表明，古细菌Lhr优先靶向DNA复制叉结构。在遗传测定中，古细菌Lhr的表达表现出与复制偶联的DNA修复酶Hel308和RecQ相同的表型。与DNA双链体，襟翼和霍利迪交界处相比，纯化的古细菌Lhr优先解绕分叉的DNA底物模型，并按方向性解绕它们。单分子FRET测量表明，Lhr与DNA叉的结合会导致在叉分支点或接近叉分支点的ATP独立畸变和碱基对解链。Lhr的ATP依赖性方向易位导致叉子DNA通过“亲本” DNA链解开。Lhr与复制叉在体内和体外的相互作用表明，它在停滞或断裂的DNA复制中有助于DNA修复。