Visualisation of inter loop tertiary base pairing and stacking interactions in an unusual slipped loop DNA structure |
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Authors: | V Lalitha and N Yathindra |
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Institution: | (1) Department of Crystallography and Biophysics, University of Madras, Guindy Campus, 600025 Madras, India |
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Abstract: | The conformation of an unusual slipped loop DNA structure exhibited by the sequence d(GAATTCCCGAATTC)2 is determined using a combination of geometrical and molecular mechanics methods. This sequence is known to form a B-DNA-like
duplex with the central non-complementary cytosines extruded into single stranded loop regions. The unusual feature is that
the interior guanine does not pair with the cytosine across, instead, it pairs with the cytosine upstream by skipping two
cytosines, leading to a slipped loop DNA structure with the loops staggered by two base pairs. The two loops, despite being
very small, can fold across minor or major groove symmetrically or asymmetrically disposed, with one of the loop bases partially
blocking the major or minor groove. Most interestingly, for certain conformations, the loop bases approach one another at
close proximity so as to engage even in base pairing as well as base stacking interactions across the major groove. While
such pairing and stacking are common in the tertiary folds of RNA, this is the first time that such an interaction is visualized
in a DNA. This observation demonstrates that a W-C pair can readily be accomplished in a typical slipped loop structure postulated
for DNA. Such tertiary loop interaction may prevent access to regulatory proteins across the major groove of the duplex DNA,
thus providing a structure-function relation for the occurrence of slipped loop structure in DNA.
Contribution no. 839 from this department |
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Keywords: | Slipped loop DNA structure unusual DNA structure inter loop base pair in DNA inter loop base stacking in DNA staggered loop DNA structure regulatory protein inhibition |
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