Ability of spermine to differentiate between DNA sequences--preferential stabilization of A-tracts.
The regulatory roles fulfilled by polyamines by governance of chromatin structure are made possible by their strong association with cellular DNA, and hence by their ability to modulate DNA structure and function. Towards this end, it is crucial to understand the manifestation of sequence-dependent polyamine binding at the secondary and tertiary structural levels of DNA. This study utilizes circular dichroism (CD) and isothermal titration calorimetry (ITC) to address this relationship by using 20bp oligonucleotides with sequences-poly(dA):poly(dT), poly(dAdT):poly(dAdT), poly(dG):poly(dC), poly(dGdC):poly(dGdC)-that yield physiologically relevant structures, and poly(dIdC):poly(dIdC). CD studies show that at physiological ionic strength (150mM NaCl), spermine preferentially stabilizes A-tracts, and increases flexibility of the G-tract oligomer; the latter is also suggested by the larger change in entropy (DeltaS) of spermine binding to G-tracts. Given the chromatin destabilizing property of these sequences, these findings suggest a role for spermine in stabilization of non-nucleosomal A-tracts, and a compensating mechanism for incorporation of G-tracts in the chromatin structure. Other implications of these findings in sequence dependent DNA packaging are discussed.
Patel
Mayank M
MM
Department of Pharmaceutical Sciences, School of Pharmacy--C238, University of Colorado Health Sciences Center, 4200 E. Ninth Avenue, Denver, CO 80262, USA. mayank.patel@uchsc.edu
Anchordoquy
Thomas J
TJ
D001483:Base Sequence; D001665:Binding Sites; D002151:Calorimetry / Q000379:methods; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry* / Q000502:physiology; D019277:Entropy; D006860:Hydrogen Bonding; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D011089:Polydeoxyribonucleotides / Q000737:chemistry*; D012680:Sensitivity and Specificity; D013096:Spermine / Q000737:chemistry* / Q000502:physiology; D017186:Titrimetry / Q000379:methods
D011089:Polydeoxyribonucleotides; D013096:Spermine; D004247:DNA