NUCLEIC ACID STRUCTURE DNA and RNA are large macromolecules with several levels of complexity Nucleotides form the repeating units Phosphodiester bonds link nucleotides to form a strand Two strands interact to form a double helix The double helix interacts with proteins resulting in 3-D structures in the form of chromatin 3D structure

Nucleotide Components Figure 9.8 9-25 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Combining all the parts Base + sugar  nucleoside Example Adenine + ribose = Adenosine Adenine + deoxyribose = Deoxyadenosine Base + sugar + phosphate(s)  nucleotide Adenosine monophosphate (AMP) Adenosine diphosphate (ADP) Adenosine triphosphate (ATP) 9-27 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

9-28 Figure 9.10 Base always attached here Phosphates are attached there Figure 9.10 9-28

Figure: 10-08 Caption: Structures and names of the nucleosides and nucleotides of RNA and DNA.

Figure: 10-09 Caption: Basic structures of nucleoside diphosphates and triphosphates, as illustrated by thymidine diphosphate and adenosine triphosphate.

dNMP NMP A, G, C or T A, G, C or U Figure 9.9 The structure of nucleotides found in (a) DNA and (b) RNA 9-26

Nucleotide Polymerization Reaction: Phosphodiester Bond Formation Figure: 11-08 Caption: Demonstration of 5’-to-3’ synthesis of DNA.

Figure 9.11 9-30 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Events Leading to DNA Structure Determination 1953, James Watson and Francis Crick discovered the double helical structure of DNA The scientific framework for their breakthrough was provided by other scientists including Linus Pauling Rosalind Franklin Erwin Chargaff 9-31 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Linus Pauling

Rosalind Franklin Helical Double stranded 10 base pairs per turn

X-ray Diffraction Pattern of DNA

Erwin Chargaff’s Experiment It was assumed the four bases: A, G, C and T were in a repeating, tetranucleotide configuration Therefore, there should be the same amount of A, G, C & T in any molecule of DNA form any source Chargaff carefully determined the exact percentages of nuceotides in DNA from several sources 9-35 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Erwin Chargaff’s Data % A = % T & %G = %C However %AT DID NOT = %GC This observation became known as Chargaff’s rule 9-39

Watson & Crick Model DNA Structure

Base Pairing Key to DNA Structure

Features of the DNA Double Helix NH 2 T 2 nm One nucleotide 0.34 nm One complete turn 3.4 nm O H N P O– NH2 OH H2N HO 5¢ end 3¢ end 3¢ hydroxyl 5¢phosphate A S C G CH2 CH3

Features of the DNA Double Helix Minor groove Minor groove Major groove Major groove Ball-and-stick model of DNA Space-filling model of DNA

Major Helical Conformations of DNA A-DNA B-DNA

Melting Point Curve: Tm is Proportional to %GC Figure: 10-14 Caption: Increase in UV absorbance and temperature (the hyperchromic effect) for two DNA molecules with different G[triple bond]C contents. The molecule with a melting point (Tm) of 83°C has a greater G[triple bond]C content than the molecule with a Tm of 77°C. Tm= 68.9 + (0.41)(%GC)

The Three-Dimensional Structure of DNA Figure 9.21 9-55

RNA Structure The primary structure of an RNA strand is much like that of a DNA strand RNA is made as a single strand only, however it may form a double stranded structures RNA strands can be a 10s to1000s of nt in length RNA is made from a DNA template - only one of the two strands of a DNA helix is used as the template RNA contains uracil rather than thymine 9-57

Figure 9.22 9-58

RNA Secondary Structures Figure 9.23 9-60

RNA Tertiary Structure – a tRNA Figure 9.24 9-61