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Nucleic Acids Res. 2018 Nov 30;46(21):11627-11638. doi: 10.1093/nar/gky902.

High-resolution DNA quadruplex structure containing all the A-, G-, C-, T-tetrads.

Author information

1
State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Department of Physiology and Biophysics, School of Life Sciences, Fudan University, Shanghai 200433, China.
2
State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Department of Biochemistry, School of Life Sciences, Fudan University, Shanghai 200433, China.
3
Department of Chemistry and The RNA Institute, University at Albany, State University of New York, Albany, NY 12222, USA.
4
State Key Laboratory of Bioorganic and Natural Product Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, Shanghai 200032, China.
5
Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China.

Abstract

DNA can form diverse structures, which predefine their physiological functions. Besides duplexes that carry the genetic information, quadruplexes are the most well-studied DNA structures. In addition to their important roles in recombination, replication, transcription and translation, DNA quadruplexes have also been applied as diagnostic aptamers and antidisease therapeutics. Herein we further expand the sequence and structure complexity of DNA quadruplex by presenting a high-resolution crystal structure of DNA1 (5'-AGAGAGATGGGTGCGTT-3'). This is the first quadruplex structure that contains all the internal A-, G-, C-, T-tetrads, A:T:A:T tetrads and bulged nucleotides in one single structure; as revealed by site-specific mutagenesis and biophysical studies, the central ATGGG motif plays important role in the quadruplex formation. Interestingly, our structure also provides great new insights into cation recognition, including the first-time reported Pb2+, by tetrad structures.

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