03992nam 22006015 450 991015532650332120200702123627.0978331945129910.1007/978-3-319-45129-9(CKB)3710000000964788(DE-He213)978-3-319-45129-9(MiAaPQ)EBC4751449(PPN)197138543(EXLCZ)99371000000096478820161130d2017 u| 0engurnn|008mamaatxtrdacontentcrdamediacrrdacarrierDynamics and Mechanism of DNA-Bending Proteins in Binding Site Recognition /by Yogambigai Velmurugu1st ed. 2017.Cham :Springer International Publishing :Imprint: Springer,2017.1 online resource (XXI, 199 p. 112 illus., 105 illus. in color.) Springer Theses, Recognizing Outstanding Ph.D. Research,2190-50533-319-45128-6 3-319-45129-4 Includes bibliographical references.Introduction -- Methods -- Integration Host Factor (IHF)-DNA interaction -- Lesion Recognition by Xeroderma Pigmentosum C (XPC) Protein -- DNA Mismatch Repair.Using a novel approach that combines high temporal resolution of the laser T-jump technique with unique sets of fluorescent probes, this study unveils previously unresolved DNA dynamics during search and recognition by an architectural DNA bending protein and two DNA damage recognition proteins. Many cellular processes involve special proteins that bind to specific DNA sites with high affinity. How these proteins recognize their sites while rapidly searching amidst ~3 billion nonspecific sites in genomic DNA remains an outstanding puzzle. Structural studies show that proteins severely deform DNA at specific sites and indicate that DNA deformability is a key factor in site-specific recognition. However, the dynamics of DNA deformations have been difficult to capture, thus obscuring our understanding of recognition mechanisms. The experiments presented in this thesis uncover, for the first time, rapid (~100-500 microseconds) DNA unwinding/bending attributed to nonspecific interrogation, prior to slower (~5-50 milliseconds) DNA kinking/bending/nucleotide-flipping during recognition. These results help illuminate how a searching protein interrogates DNA deformability and eventually “stumbles” upon its target site. Submillisecond interrogation may promote preferential stalling of the rapidly scanning protein at cognate sites, thus enabling site-recognition. Such multi-step search-interrogation-recognition processes through dynamic conformational changes may well be common to the recognition mechanisms for diverse DNA-binding proteins. .Springer Theses, Recognizing Outstanding Ph.D. Research,2190-5053BiophysicsBiophysicsSpectrum analysisMicroscopyProteinsBiological and Medical Physics, Biophysicshttps://scigraph.springernature.com/ontologies/product-market-codes/P27008Spectroscopy and Microscopyhttps://scigraph.springernature.com/ontologies/product-market-codes/P31090Protein-Ligand Interactionshttps://scigraph.springernature.com/ontologies/product-market-codes/L14060Biophysics.Biophysics.Spectrum analysis.Microscopy.Proteins.Biological and Medical Physics, Biophysics.Spectroscopy and Microscopy.Protein-Ligand Interactions.571.4Velmurugu Yogambigaiauthttp://id.loc.gov/vocabulary/relators/aut819544BOOK9910155326503321Dynamics and Mechanism of DNA-Bending Proteins in Binding Site Recognition1826398UNINA