Levikova Maryna, Pinto Cosimo, Cejka Petr
Institute of Molecular Cancer Research, University of Zurich, 8057 Zurich, Switzerland.
Institute for Research in Biomedicine, Università della Svizzera italiana, 6500 Bellinzona, Switzerland.
Genes Dev. 2017 Mar 1;31(5):493-502. doi: 10.1101/gad.295196.116. Epub 2017 Mar 23.
DNA2 nuclease-helicase functions in DNA replication and recombination. This requires the nuclease of DNA2, while, in contrast, the role of the helicase activity has been unclear. We now show that the motor activity of both recombinant yeast and human DNA2 promotes efficient degradation of long stretches of ssDNA, particularly in the presence of the replication protein A. This degradation is further stimulated by a direct interaction with a cognate RecQ family helicase, which functions with DNA2 in DNA end resection to initiate homologous recombination. Consequently, helicase-deficient yeast cells display reduced resection speed of HO-induced DNA double-strand breaks. These results support a model of DNA2 and the RecQ family helicase partner forming a bidirectional motor machine, where the RecQ family helicase is the lead helicase, and the motor of DNA2 functions as a ssDNA translocase to promote degradation of 5'-terminated DNA.
DNA2核酸酶解旋酶在DNA复制和重组过程中发挥作用。这需要DNA2的核酸酶功能，而相比之下，解旋酶活性的作用一直不清楚。我们现在表明，重组酵母和人类DNA2的动力活性都能促进长片段单链DNA的有效降解，特别是在复制蛋白A存在的情况下。与同源RecQ家族解旋酶的直接相互作用进一步刺激了这种降解，该解旋酶在DNA末端切除过程中与DNA2协同作用以启动同源重组。因此，解旋酶缺陷的酵母细胞显示出HO诱导的DNA双链断裂的切除速度降低。这些结果支持了一个模型，即DNA2和RecQ家族解旋酶伙伴形成一个双向动力机器，其中RecQ家族解旋酶是主导解旋酶，而DNA2的动力则作为单链DNA转位酶促进5'端DNA的降解。
