Interaction of the Zα domain of human ADAR1 with a negatively supercoiled plasmid visualized by atomic force microscopy

Alexander Y. Lushnikov, Bernard A. Brown, Elena A. Oussatcheva, Vladimir N. Potaman, Richard R. Sinden, Yuri L Lyubchenko

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Interest to the left-handed DNA conformation has been recently boosted by the findings that a number of proteins contain the Zα domain, which has been shown to specifically recognize Z-DNA. The biological function of Zα 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 Zα domain in isolation. We have hypothesized that the recognition of a Z-DNA sequence by the Zα ADAR1 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 Zα ADAR1 complexed with supercoiled plasmid DNAs. We have demonstrated that the ZαADAR1 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 Zα 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 ZαADAR1 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.

Original languageEnglish (US)
Pages (from-to)4704-4712
Number of pages9
JournalNucleic acids research
Volume32
Issue number15
DOIs
StatePublished - Oct 15 2004

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Z-Form DNA
Atomic Force Microscopy
Plasmids
Nucleic Acid Conformation
Superhelical DNA
Biological Phenomena
DNA-Binding Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

Interaction of the Zα domain of human ADAR1 with a negatively supercoiled plasmid visualized by atomic force microscopy. / Lushnikov, Alexander Y.; Brown, Bernard A.; Oussatcheva, Elena A.; Potaman, Vladimir N.; Sinden, Richard R.; Lyubchenko, Yuri L.

In: Nucleic acids research, Vol. 32, No. 15, 15.10.2004, p. 4704-4712.

Research output: Contribution to journalArticle

Lushnikov, Alexander Y. ; Brown, Bernard A. ; Oussatcheva, Elena A. ; Potaman, Vladimir N. ; Sinden, Richard R. ; Lyubchenko, Yuri L. / Interaction of the Zα domain of human ADAR1 with a negatively supercoiled plasmid visualized by atomic force microscopy. In: Nucleic acids research. 2004 ; Vol. 32, No. 15. pp. 4704-4712.
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