title: Shuttling along DNA and directed processing of D-loops by RecQ helicase support quality control of homologous recombination.
abstract: Cells must continuously repair inevitable DNA damage while avoiding the deleterious consequences of imprecise repair. Distinction between legitimate and illegitimate repair processes is thought to be achieved in part through differential recognition and processing of specific noncanonical DNA structures, although the mechanistic basis of discrimination remains poorly defined. Here, we show that Escherichia coli RecQ, a central DNA recombination and repair enzyme, exhibits differential processing of DNA substrates based on their geometry and structure. Through single-molecule and ensemble biophysical experiments, we elucidate how the conserved domain architecture of RecQ supports geometry-dependent shuttling and directed processing of recombination-intermediate [displacement loop (D-loop)] substrates. Our study shows that these activities together suppress illegitimate recombination in vivo, whereas unregulated duplex unwinding is detrimental for recombination precision. Based on these results, we propose a mechanism through which RecQ helicases achieve recombination precision and efficiency.
authors.affiliation: Department of Biochemistry, Eötvös Loránd University-Hungarian Academy of Sciences "Momentum" Motor Enzymology Research Group, Eötvös Loránd University, H-1117 Budapest, Hungary.
authors.forename: Gábor M
authors.initials: GM
authors.lastname: Harami
authors.affiliation: Laboratory of Single Molecule Biophysics, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Yeonee
authors.initials: Y
authors.lastname: Seol
authors.affiliation: Laboratory of Single Molecule Biophysics, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Junghoon
authors.initials: J
authors.lastname: In
authors.affiliation: Department of Biochemistry, Eötvös Loránd University-Hungarian Academy of Sciences "Momentum" Motor Enzymology Research Group, Eötvös Loránd University, H-1117 Budapest, Hungary.
authors.forename: Veronika
authors.initials: V
authors.lastname: Ferencziová
authors.affiliation: Department of Biochemistry, Eötvös Loránd University-Hungarian Academy of Sciences "Momentum" Motor Enzymology Research Group, Eötvös Loránd University, H-1117 Budapest, Hungary.
authors.forename: Máté
authors.initials: M
authors.lastname: Martina
authors.affiliation: Department of Biochemistry, Eötvös Loránd University-Hungarian Academy of Sciences "Momentum" Motor Enzymology Research Group, Eötvös Loránd University, H-1117 Budapest, Hungary.
authors.forename: Máté
authors.initials: M
authors.lastname: Gyimesi
authors.affiliation: Department of Biochemistry, Eötvös Loránd University-Hungarian Academy of Sciences "Momentum" Motor Enzymology Research Group, Eötvös Loránd University, H-1117 Budapest, Hungary.
authors.forename: Kata
authors.initials: K
authors.lastname: Sarlós
authors.affiliation: Department of Biochemistry, Eötvös Loránd University-Hungarian Academy of Sciences "Momentum" Motor Enzymology Research Group, Eötvös Loránd University, H-1117 Budapest, Hungary.
authors.forename: Zoltán J
authors.initials: ZJ
authors.lastname: Kovács
authors.affiliation: Department of Biochemistry, Eötvös Loránd University-Hungarian Academy of Sciences "Momentum" Motor Enzymology Research Group, Eötvös Loránd University, H-1117 Budapest, Hungary.
authors.forename: Nikolett T
authors.initials: NT
authors.lastname: Nagy
authors.affiliation: Laboratory of Single Molecule Biophysics, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Yuze
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Genetics, Eötvös Loránd University, H-1117 Budapest, Hungary.
authors.forename: Tibor
authors.initials: T
authors.lastname: Vellai
authors.affiliation: Laboratory of Single Molecule Biophysics, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892; mihaly.kovacs@ttk.elte.hu neumankc@mail.nih.gov.
authors.forename: Keir C
authors.initials: KC
authors.lastname: Neuman
authors.affiliation: Department of Biochemistry, Eötvös Loránd University-Hungarian Academy of Sciences "Momentum" Motor Enzymology Research Group, Eötvös Loránd University, H-1117 Budapest, Hungary; mihaly.kovacs@ttk.elte.hu neumankc@mail.nih.gov.
authors.forename: Mihály
authors.initials: M
authors.lastname: Kovács
mesh_terms: D004247:DNA / Q000378:metabolism*; D004260:DNA Repair; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism*; D059765:Homologous Recombination; D055029:Inverted Repeat Sequences; D053484:RecQ Helicases / Q000737:chemistry / Q000378:metabolism*
chemical_list: D029968:Escherichia coli Proteins; D004247:DNA; C506724:RecQ protein, E coli; D053484:RecQ Helicases
keywords: DNA unwinding; RecQ; helicase; magnetic tweezers; single molecule