title: BLM unfolds G-quadruplexes in different structural environments through different mechanisms.
abstract: Mutations in the RecQ DNA helicase gene BLM give rise to Bloom's syndrome, which is a rare autosomal recessive disorder characterized by genetic instability and cancer predisposition. BLM helicase is highly active in binding and unwinding G-quadruplexes (G4s), which are physiological targets for BLM, as revealed by genome-wide characterizations of gene expression of cells from BS patients. With smFRET assays, we studied the molecular mechanism of BLM-catalyzed G4 unfolding and showed that ATP is required for G4 unfolding. Surprisingly, depending on the molecular environments of G4, BLM unfolds G4 through different mechanisms: unfolding G4 harboring a 3'-ssDNA tail in three discrete steps with unidirectional translocation, and unfolding G4 connected to dsDNA by ssDNA in a repetitive manner in which BLM remains anchored at the ss/dsDNA junction, and G4 was unfolded by reeling in ssDNA. This indicates that one BLM molecule may unfold G4s in different molecular environments through different mechanisms.
authors.affiliation: College of Life Sciences, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Wen-Qiang
authors.initials: WQ
authors.lastname: Wu
authors.affiliation: College of Life Sciences, Northwest A&F University, Yangling, Shaanxi 712100, China xxi01@ens-cachan.fr.
authors.forename: Xi-Miao
authors.initials: XM
authors.lastname: Hou
authors.affiliation: Beijing National Laboratory for Condensed Matter Physics and CAS Key Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Beijing National Laboratory for Condensed Matter Physics and CAS Key Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Shuo-Xing
authors.initials: SX
authors.lastname: Dou
authors.affiliation: College of Life Sciences, Northwest A&F University, Yangling, Shaanxi 712100, China Laboratoire de Biologie et Pharmacologie Appliquée, Ecole Normale Supérieure de Cachan, Centre National de la Recherche Scientifique, 61 Avenue du Président Wilson, 94235 Cachan, France xxi01@ens-cachan.fr.
authors.forename: Xu-Guang
authors.initials: XG
authors.lastname: Xi
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D054856:G-Quadruplexes; D053484:RecQ Helicases / Q000378:metabolism*
chemical_list: D004277:DNA, Single-Stranded; D000255:Adenosine Triphosphate; D004247:DNA; C097151:Bloom syndrome protein; D053484:RecQ Helicases