Attenuation of DNA-protein interactions associated with intrinsic, sequence-dependent DNA curvature.
Inherently curved DNA segments, associated with short runs of adenines, have been identified in many gene regulatory regions, yet their physiological significance remains unknown. The observations reported in this study indicate that intrinsically bent nucleic acid fragments are characterized by substantially attenuated affinities toward DNA-binding proteins involved in structural functions, such as H1 histone and protamine, as well as toward various DNA-modifying enzymes including ligases and exo- and endonucleases. Two mechanisms might be responsible for the altered binding properties. According to the first mechanism, the attenuated binding affinities and the bending represent two independent consequences of the unique structural parameters exhibited by A-tracts. Indeed, analysis of the degradation products obtained upon exposure of the curved sequences to various chemical nucleases points toward the narrowing of the DNA minor groove, a conformational modulation known to characterize A-tracts and to run along the axially-bent motifs, as a potential determinant of the observed binding attenuation. Alternatively, the conformational constraints which result from the stable bending might act to modulate the strength of DNA-protein interactions. Although the factor directly responsible for the altered binding affinities revealed by the bent sequences cannot as yet be conclusively resolved, it is proposed that a reiteration of this specific factor, being either an A-tract or a bend, in phase with the DNA helical repeat acts to amplify the modulation of the binding.(ABSTRACT TRUNCATED AT 250 WORDS)
Shatzky-Schwartz
M
M
Department of Organic Chemistry, Weizmann Institute of Science, Rehovot, Israel.
Hiller
Y
Y
Reich
Z
Z
Ghirlando
R
R
Weinberger
S
S
Minsky
A
A
D000227:Adenine Nucleotides / Q000737:chemistry; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D004247:DNA / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D007700:Kinetics; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D012091:Repetitive Sequences, Nucleic Acid; D013329:Structure-Activity Relationship
D000227:Adenine Nucleotides; D004268:DNA-Binding Proteins; D004247:DNA