Lucic, Bojana, Zhang, Ying, King, Oliver, Mendoza-Maldonado, Ramiro, Berti, Matteo, Niesen, Frank H., Burgess-Brown, Nicola A., Pike, Ashley C.W., Cooper, Christopher D.O., Gileadi, Opher and Vindigni, Alessandro (2011) A prominent β-hairpin structure in the winged-helix domain of RECQ1 is required for DNA unwinding and oligomer formation. Nucleic Acids Research, 39 (5). pp. 1703-1717. ISSN 0305-1048
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RecQ helicases have attracted considerable interest in recent years due to their role in the suppression of genome instability and human diseases. These atypical helicases exert their function by resolving a number of highly specific DNA structures. The crystal structure of a truncated catalytic core of the human RECQ1 helicase (RECQ1(49-616)) shows a prominent β-hairpin, with an aromatic residue (Y564) at the tip, located in the C-terminal winged-helix domain. Here, we show that the β-hairpin is required for the DNA unwinding and Holliday junction (HJ) resolution activity of full-length RECQ1, confirming that it represents an important determinant for the distinct substrate specificity of the five human RecQ helicases. In addition, we found that the β-hairpin is required for dimer formation in RECQ1(49-616) and tetramer formation in full-length RECQ1. We confirmed the presence of stable RECQ1(49-616) dimers in solution and demonstrated that dimer formation favours DNA unwinding; even though RECQ1 monomers are still active. Tetramers are instead necessary for more specialized activities such as HJ resolution and strand annealing. Interestingly, two independent protein-protein contacts are required for tetramer formation, one involves the β-hairpin and the other the N-terminus of RECQ1, suggesting a non-hierarchical mechanism of tetramer assembly.
|Subjects:||Q Science > QH Natural history > QH301 Biology|
|Schools:||School of Applied Sciences|
|Depositing User:||Christopher Cooper|
|Date Deposited:||23 Nov 2015 12:41|
|Last Modified:||11 Dec 2015 22:18|
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