| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Swuec, Paolo Von Delft, Frank Gileadi, Opher Schnecke, Christina Zhang, Ying Costa, Alessandro Gomathinayagam, Shivasankari Marino, Francesca Pike, Ashley C. W. Berti, Matteo Vindigni, Alessandro Renault, Ludovic |
| Description |
Author Affiliation: Pike AC ( Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, United Kingdom); Gomathinayagam S ( Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO 63104); Swuec P ( Cancer Research UK Clare Hall Laboratories, South Mimms EN6 3LD, United Kingdom); Berti M ( Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO 63104); Zhang Y ( Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, United Kingdom); Schnecke C ( Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, United Kingdom); Marino F ( Structural Biology Laboratory, Sincrotrone Trieste, Trieste 34149, Italy.); von Delft F ( Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, United Kingdom); Renault L ( Cancer Research UK Clare Hall Laboratories, South Mimms EN6 3LD, United Kingdom); Costa A ( Cancer Research UK Clare Hall Laboratories, South Mimms EN6 3LD, United Kingdom); Gileadi O ( Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, United Kingdom); Vindigni A ( Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO 63104); |
| Abstract |
RecQ helicases are a widely conserved family of ATP-dependent motors with diverse roles in nearly every aspect of bacterial and eukaryotic genome maintenance. However, the physical mechanisms by which RecQ helicases recognize and process specific DNA replication and repair intermediates are largely unknown. Here, we solved crystal structures of the human RECQ1 helicase in complexes with tailed-duplex DNA and ssDNA. The structures map the interactions of the ssDNA tail and the branch point along the helicase and Zn-binding domains, which, together with reported structures of other helicases, define the catalytic stages of helicase action. We also identify a strand-separating pin, which (uniquely in RECQ1) is buttressed by the protein dimer interface. A duplex DNA-binding surface on the C-terminal domain is shown to play a role in DNA unwinding, strand annealing, and Holliday junction (HJ) branch migration. We have combined EM and analytical ultracentrifugation approaches to show that RECQ1 can form what appears to be a flat, homotetrameric complex and propose that RECQ1 tetramers are involved in HJ recognition. This tetrameric arrangement suggests a platform for coordinated activity at the advancing and receding duplexes of an HJ during branch migration. |
| ISSN |
00278424 |
| e-ISSN |
10916490 |
| Journal |
Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number |
14 |
| Volume Number |
112 |
| Language |
English |
| Publisher |
National Academy of Sciences |
| Publisher Date |
2015-04-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
DNA Helicases Chemistry DNA RecQ Helicases Animals Chromatography, Gel Crystallization Crystallography, X-Ray DNA, Cruciform Physiology DNA, Single-Stranded Escherichia Coli Metabolism Insects Molecular Conformation Nucleic Acid Denaturation Nucleotides Protein Binding Protein Structure, Tertiary Zinc Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Multidisciplinary |
