The motor activity of DNA2 functions as an ssDNA translocase to promote DNA end resection.
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 yeastdna2 K1080Ecells 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.
Institute of Molecular Cancer Research, University of Zurich, 8057 Zurich, Switzerland.
Maryna
M
Levikova
Institute of Molecular Cancer Research, University of Zurich, 8057 Zurich, Switzerland.
Cosimo
C
Pinto
Institute of Molecular Cancer Research, University of Zurich, 8057 Zurich, Switzerland.|Institute for Research in Biomedicine, Università della Svizzera italiana, 6500 Bellinzona, Switzerland.
Petr
P
Cejka
D059766:DNA End-Joining Repair / Q000235:genetics / Q000502:physiology*; D004265:DNA Helicases / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000378:metabolism*; D059765:Homologous Recombination; D006801:Humans; D053484:RecQ Helicases / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D051716:Replication Protein A / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics
D004277:DNA, Single-Stranded; D011994:Recombinant Proteins; D051716:Replication Protein A; D004265:DNA Helicases; D053484:RecQ Helicases
DNA end resection; DNA helicase; DNA nuclease; hDNA2; ssDNA translocase; yDna2