A thermodynamic overview of naturally occurring intramolecular DNA quadruplexes.

Abstract:

:Loop length and its composition are important for the structural and functional versatility of quadruplexes. To date studies on the loops have mainly concerned model sequences compared with naturally occurring quadruplex sequences which have diverse loop lengths and compositions. Herein, we have characterized 36 quadruplex-forming sequences from the promoter regions of various proto-oncogenes using CD, UV and native gel electrophoresis. We examined folding topologies and determined the thermodynamic profile for quadruplexes varying in total loop length (5-18 bases) and composition. We found that naturally occurring quadruplexes have variable thermodynamic stabilities (DeltaG(37)) ranging from -1.7 to -15.6 kcal/mol. Overall, our results suggest that both loop length and its composition affect quadruplex structure and thermodynamics, thus making it difficult to draw generalized correlations between loop length and thermodynamic stability. Additionally, we compared the thermodynamic stability of quadruplexes and their respective duplexes to understand quadruplex-duplex competition. Our findings invoke a discussion on whether biological function is associated with quadruplexes with lower thermodynamic stability which undergo facile formation and disruption, or by quadruplexes with high thermodynamic stability.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Kumar N,Maiti S

doi

10.1093/nar/gkn543

subject

Has Abstract

pub_date

2008-10-01 00:00:00

pages

5610-22

issue

17

eissn

0305-1048

issn

1362-4962

pii

gkn543

journal_volume

36

pub_type

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