Structural polymorphism exhibited by a quasipalindrome present in the locus control region (LCR) of the human beta-globin gene cluster.
Structural polymorphism of DNA is a widely accepted property. A simple addition to this perception has been our recent finding, where a single nucleotide polymorphism (SNP) site present in a quasipalindromic sequence of beta-globin LCR exhibited a hairpin-duplex equilibrium. Our current studies explore that secondary structures adopted by individual complementary strands compete with formation of a perfect duplex. Using gel-electrophoresis, ultraviolet (UV)-thermal denaturation, circular dichroism (CD) techniques, we have demonstrated the structural transitions within a perfect duplex containing 11 bp quasipalindromic stretch (TGGGG(G/C)CCCCA), to hairpins and bulge duplex forms. The extended version of the 11 bp duplex, flanked by 5 bp on both sides also demonstrated conformational equilibrium between duplex and hairpin species. Gel-electrophoresis confirms that the duplex coexists with hairpin and bulge duplex/cruciform species. Further, in CD spectra of duplexes, presence of two overlapping positive peaks at 265 and 285 nm suggest the features of A- as well as B-type DNA conformation and show oligomer concentration dependence, manifested in A --> B transition. This indicates the possibility of an architectural switching at quasipalindromic region between linear duplex to a cruciform structure. Such DNA structural variations are likely to be found in the mechanics of molecular recognition and manipulation by proteins.
Kaushik
Mahima
M
Nucleic Acids Research Laboratory, Department of Chemistry, University of Delhi (North Campus), Delhi 110007, India.
Kukreti
Shrikant
S
D001483:Base Sequence; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry; D045566:DNA, Cruciform / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D005914:Globins / Q000235:genetics*; D006801:Humans; D019901:Locus Control Region; D005810:Multigene Family; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature
D045566:DNA, Cruciform; D005914:Globins; D004247:DNA