1] Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016, USA [2].
1] Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016, USA [2] Howard Hughes Medical Institute, New York University School of Medicine, New York, New York 10016, USA [3].
Nature. 2014 Jan 16;505(7483):372-7. doi: 10.1038/nature12928. Epub 2014 Jan 8.
UvrD helicase is required for nucleotide excision repair, although its role in this process is not well defined. Here we show that Escherichia coli UvrD binds RNA polymerase during transcription elongation and, using its helicase/translocase activity, forces RNA polymerase to slide backward along DNA. By inducing backtracking, UvrD exposes DNA lesions shielded by blocked RNA polymerase, allowing nucleotide excision repair enzymes to gain access to sites of damage. Our results establish UvrD as a bona fide transcription elongation factor that contributes to genomic integrity by resolving conflicts between transcription and DNA repair complexes. Furthermore, we show that the elongation factor NusA cooperates with UvrD in coupling transcription to DNA repair by promoting backtracking and recruiting nucleotide excision repair enzymes to exposed lesions. Because backtracking is a shared feature of all cellular RNA polymerases, we propose that this mechanism enables RNA polymerases to function as global DNA damage scanners in bacteria and eukaryotes.
UvrD 解旋酶对于核苷酸切除修复是必需的，尽管其在该过程中的作用尚未明确。在这里，我们表明大肠杆菌 UvrD 在转录延伸过程中与 RNA 聚合酶结合，并利用其解旋酶/转位酶活性迫使 RNA 聚合酶沿着 DNA 向后滑动。通过诱导回溯，UvrD 暴露出被受阻 RNA 聚合酶屏蔽的 DNA 损伤，使核苷酸切除修复酶能够进入损伤部位。我们的结果确立了 UvrD 作为一种真正的转录延伸因子，通过解决转录和 DNA 修复复合物之间的冲突，有助于基因组的完整性。此外，我们表明，伸长因子 NusA 通过促进回溯和招募核苷酸切除修复酶到暴露的损伤部位，与 UvrD 一起在将转录与 DNA 修复偶联中发挥作用。由于回溯是所有细胞 RNA 聚合酶的共同特征，我们提出这种机制使 RNA 聚合酶能够在细菌和真核生物中充当全局 DNA 损伤扫描器。
