Abstract
Aprataxin is a DNA deadenylase that resolves DNA 5′-AMP termini and reverses abortive DNA ligation. The crystal structures of Schizosaccharomyces pombe aprataxin Hnt3 in its apo form and in complex to dsDNA and dsDNA–AMP reveal how Hnt3 recognizes and processes 5′-adenylated DNA in a structure-specific manner. The bound DNA adopts a 5′-flap conformation that facilitates 5′-AMP access to the active site, where AMP cleavage occurs by a canonical catalytic mechanism.
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Acknowledgements
We are grateful to Y. Chen for her assistance in Biacore analysis. We thank the staff at the Shanghai Synchrotron Radiation Facility beamline 17U for assistance with data collection, and we thank our colleagues for critical comments on the manuscript. This work was funded by Chinese Ministry of Science and Technology '973' grants 2011CB910302 and 2011CB910304 to T.J. and D.-C.W.; National Natural Science Foundation of China grants 31021062 and 31025009 to T.J. and 31000330 to D.Z.; and Chinese Academy of Sciences grant KSCX2-EW-J-3 to J.D. and D.-C.W.
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Y.G., D.Z., J.D., T.J. and D.-C.W. designed the research; Y.G., D.Z., J.D., X.R. and C.-N.D. carried out the experiments; Y.G., D.Z., J.D., T.J. and D.-C.W. analyzed the data and wrote the paper; and all authors contributed to editing the manuscript.
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Gong, Y., Zhu, D., Ding, J. et al. Crystal structures of aprataxin ortholog Hnt3 reveal the mechanism for reversal of 5′-adenylated DNA. Nat Struct Mol Biol 18, 1297–1299 (2011). https://doi.org/10.1038/nsmb.2145
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DOI: https://doi.org/10.1038/nsmb.2145
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