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Title: Disruption of energetic and dynamic base pairing cooperativity in DNA duplexes by an abasic site
DNA duplex stability arises from cooperative interactions between multiple adjacent nucleotides that favor base pairing and stacking when formed as a continuous stretch rather than individually. Lesions and nucleobase modifications alter this stability in complex manners that remain challenging to understand despite their centrality to biology. Here, we investigate how an abasic site destabilizes small DNA duplexes and reshapes base pairing dynamics and hybridization pathways using temperature-jump infrared spectroscopy and coarse-grained molecular dynamics simulations. We show how an abasic site splits the cooperativity in a short duplex into two segments, which destabilizes small duplexes as a whole and enables metastable half-dissociated configurations. Dynamically, it introduces an additional barrier to hybridization by constraining the hybridization mechanism to a step-wise process of nucleating and zipping a stretch on one side of the abasic site and then the other.  more » « less
Award ID(s):
2152521 2155027
NSF-PAR ID:
10403900
Author(s) / Creator(s):
; ; ;
Date Published:
Journal Name:
Proceedings of the National Academy of Sciences
Volume:
120
Issue:
14
ISSN:
0027-8424
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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