Polymorphic G:G mismatches act as hotspots for inducing right-handed Z DNA by DNA intercalation

Nucleic Acids Research
Roshan SatangeMing-Hon Hou

Abstract

DNA mismatches are highly polymorphic and dynamic in nature, albeit poorly characterized structurally. We utilized the antitumour antibiotic CoII(Chro)2 (Chro = chromomycin A3) to stabilize the palindromic duplex d(TTGGCGAA) DNA with two G:G mismatches, allowing X-ray crystallography-based monitoring of mismatch polymorphism. For the first time, the unusual geometry of several G:G mismatches including syn-syn, water mediated anti-syn and syn-syn-like conformations can be simultaneously observed in the crystal structure. The G:G mismatch sites of the d(TTGGCGAA) duplex can also act as a hotspot for the formation of alternative DNA structures with a GC/GA-5' intercalation site for binding by the GC-selective intercalator actinomycin D (ActiD). Direct intercalation of two ActiD molecules to G:G mismatch sites causes DNA rearrangements, resulting in backbone distortion to form right-handed Z-DNA structures with a single-step sharp kink. Our study provides insights on intercalators-mismatch DNA interactions and a rationale for mismatch interrogation and detection via DNA intercalation.

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Methods Mentioned

BETA
electrophoresis
surface
chip
fluorescence spectroscopy
X-ray
nuclear magnetic resonance
NMR

Software Mentioned

BIA
Phaser MR
PHENIX suite
PyMOL
Web
MIFit
3DNA
PHENIX
2000
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