title: Mechanism for accurate, protein-assisted DNA annealing by Deinococcus radiodurans DdrB.
abstract: Accurate pairing of DNA strands is essential for repair of DNA double-strand breaks (DSBs). How cells achieve accurate annealing when large regions of single-strand DNA are unpaired has remained unclear despite many efforts focused on understanding proteins, which mediate this process. Here we report the crystal structure of a single-strand annealing protein [DdrB (DNA damage response B)] in complex with a partially annealed DNA intermediate to 2.2 Å. This structure and supporting biochemical data reveal a mechanism for accurate annealing involving DdrB-mediated proofreading of strand complementarity. DdrB promotes high-fidelity annealing by constraining specific bases from unauthorized association and only releases annealed duplex when bound strands are fully complementary. To our knowledge, this mechanism provides the first understanding for how cells achieve accurate, protein-assisted strand annealing under biological conditions that would otherwise favor misannealing.
authors.affiliation: Department of Biochemistry and Biomedical Sciences and M. G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, L8N 3Z5, Canada;
authors.forename: Seiji N
authors.initials: SN
authors.lastname: Sugiman-Marangos
authors.affiliation: Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, L8S 4L8, Canada;
authors.forename: Yoni M
authors.initials: YM
authors.lastname: Weiss
authors.affiliation: Department of Biochemistry and Biomedical Sciences and M. G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, L8N 3Z5, Canada; Schulich School of Medicine and Dentistry, Department of Biochemistry, University of Western Ontario, London, ON, N6A 5C1, Canada mjunop@uwo.ca.
authors.forename: Murray S
authors.initials: MS
authors.lastname: Junop
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000502:physiology*; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D034301:Deinococcus / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins
keywords: DNA repair; DdrB; Deinococcus radiodurans; crystal structure; single-strand DNA annealing