Part I Human Genome: • Human genome project; genes on human chromosomes • Human genome sequencing; Highthroughput sequencing technology Canonical DNA: • • • • • Chemical structure and properties of B-DNA Enzymes that function on B-DNA DNA dissociation and reassociation kinetics of B-DNA Chromicity of B-DNA Major and minor grooves and DNA-protein interaction in gene regulation of B-DNA
Non-canonical DNA: • Structure of A-DNA and Z-DNA; Comparison of A, B and Z-DNA; • Discovery of Z-DNA in vitro and in living cells; • Z-DNA and human genetic diseases
Role of Major and Minor Grooves in Gene Regulation Major Groove Helix‐turn‐helix (HTH) Motif and Homeodomain proteins (hox or HOM gene cluster)
Properties of a B‐DNA Double Helix
Major grooves are the primary access points for regulatory proteins to recognize genes
Major grooves are the primary access points for regulatory proteins to recognize genes AXIS
Significance of the Major and the Minor Grooves on dsDNA Chemical groups exposed in the major and the minor grooves from the edge of the base pairs. The letters in red identify the following: hydrogen bond acceptors (A); • • hydrogen bond donors (D); • non‐polar hydrogens (H); and • methyl groups (M). Based on the distribution of A, D H and M in the major grooves, the following codes can be derived: A:T bp = A D A M G:C bp = A A D H T:A bp = M A D A C:G bp = H D A A The base distribution of the minor grooves presents no variation: A:T and T:A bp = A H A G:C and C:G bp = A D A In all cases, the code of the chemical groups in the major grooves specifies the identity of the base pair. These patterns are important because they allow proteins to unambiguously recognize DNA sequences without having to open and thereby disrupt the double helix. However the principle decoding mechanism relies upon the ability of amino acid side chains to protrude into the major groove and to recognize and bind to specific DNA sequences. In general, the minor...
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