State Key Laboratory of Biobased Material and Green Papermaking, School of Bioengineering, Qilu University of Technology, Jinan 250353, China.
Key Laboratory of Shandong Microbial Engineering, Shandong Academy of Sciences, Qilu University of Technology, Jinan 250353, China.
Int J Mol Sci. 2022 Jun 14;23(12):6631. doi: 10.3390/ijms23126631.
As an ATP-dependent DNA helicase, human ChlR1/DDX11 (Chl1 in yeast) can unwind both DNA:RNA and DNA:DNA substrates in vitro. Studies have demonstrated that ChlR1 plays a vital role in preserving genome stability by participating in DNA repair and sister chromatid cohesion, whereas the ways in which the biochemical features of ChlR1 function in DNA metabolism are not well understood. Here, we illustrate that Chl1 localizes to double-strand DNA break (DSB) sites and restrains DNA:RNA hybrid accumulation at these loci. Mutation of Chl1 strongly impairs DSB repair capacity by homologous recombination (HR) and nonhomologous end-joining (NHEJ) pathways, and deleting RNase H further reduces DNA repair efficiency, which indicates that the enzymatic activities of Chl1 are needed in . In addition, we found that the Rpc37 subunit of RNA polymerase III (RNA Pol III) interacts directly with Chl1 and that deletion of Chl1 has no influence on the localization of Rpc37 at DSB site, implying the role of Rpc37 in the recruitment of Chl1 to this site.
作为一种 ATP 依赖的 DNA 解旋酶，人类 ChlR1/DDX11（酵母中的 Chl1）可以在体外解开 DNA:RNA 和 DNA:DNA 底物。研究表明，ChlR1 通过参与 DNA 修复和姐妹染色单体黏合，在维持基因组稳定性方面发挥着重要作用，然而，ChlR1 的生化特性如何在 DNA 代谢中发挥作用尚不清楚。在这里，我们表明 Chl1 定位于双链 DNA 断裂 (DSB) 位点，并抑制这些位点处 DNA:RNA 杂交体的积累。Chl1 的突变强烈削弱了同源重组 (HR) 和非同源末端连接 (NHEJ) 途径的 DSB 修复能力，而删除 RNase H 进一步降低了 DNA 修复效率，这表明 Chl1 的酶活性在. 此外，我们发现 RNA 聚合酶 III (RNA Pol III) 的 Rpc37 亚基与 Chl1 直接相互作用，并且 Chl1 的缺失对 Rpc37 在 DSB 位点的定位没有影响，这意味着 Rpc37 在 Chl1 招募到该位点中的作用。
