Published online 1 September 2004
Nucleic Acids Research, Vol. 32 No. 15 © Oxford University Press 2004; all rights reserved
Interaction of the Z
domain of human ADAR1 with a negatively supercoiled plasmid visualized by atomic force microscopy
School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA, 1 Department of Chemistry, Wake Forest University, Winston-Salem, NC 27109, USA and 2 Institute of Biosciences and Technology, Texas A&M University System Health Sciences Center, Houston, TX 77030, USA
* To whom correspondence should be addressed at present address. Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE 68198-6025, USA. Tel: +1 402 559 1971; Fax: +1 402 559 9543; Email: ylyubchenko{at}unmc.edu
Present address: Alexander Y. Lushnikov, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE 68198-6025, USA
Received April 29, 2004; Revised June 14, 2004; Accepted August 18, 2004
Interest to the left-handed DNA conformation has been recently boosted by the findings that a number of proteins contain the Z
domain, which has been shown to specifically recognize Z-DNA. The biological function of Z is presently unknown, but it has been suggested that it may specifically direct protein regions of Z-DNA induced by negative supercoiling in actively transcribing genes. Many studies, including a crystal structure in complex with Z-DNA, have focused on the human ADAR1 Z domain in isolation. We have hypothesized that the recognition of a Z-DNA sequence by the ZADAR1 domain is context specific, occurring under energetic conditions, which favor Z-DNA formation. To test this hypothesis, we have applied atomic force microscopy to image ZADAR1 complexed with supercoiled plasmid DNAs. We have demonstrated that the ZADAR1 binds specifically to Z-DNA and preferentially to d(CG)n inserts, which require less energy for Z-DNA induction compared to other sequences. A notable finding is that site-specific Z binding to d(GC)13 or d(GC)2C(GC)10 inserts is observed when DNA supercoiling is insufficient to induce Z-DNA formation. These results indicate that ZADAR1 binding facilities the B-to-Z transition and provides additional support to the model that Z-DNA binding proteins may regulate biological processes through structure-specific recognition.
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