MCB 201 Gene Expression - Spring Semester 2004

Lecture 2 ( Structure of Nucleic Acids)

 

1. Topics

2. Overview of DNA structure:

A. Figure 4-3, Lodish5e: The DNA double helix.
a) Space-filling model of the B form, the most common form of DNA in cells. Note the sugar-phosphate backbones spiraling on the outside of the structure, the major and minor grooves, and the uniform diameter of the helix. (Note Figure 2-2 lodish5e, 2-8 Lodish5e: Space filling model based on van der Waals radii , ball and stick model, and structural formula). Compare relative bond/interaction energies using Figure 2-4, Lodish5e.
b) Four complementary base pairs are shown. Note that the two strands run in opposite directions and each base pair is held together by either two or three hydrogen bonds. The base-pairing shown follows Chargaff's rules: A-T, G-C, adenine, thymine, guanine, cytosine (N bases). Chargaff's rules were based on determinations of the chemical composition of DNA and the observation that the mol % of A and T were almost the same, as was G and C.
RNA has a similar structure, just add an OH group to 2' sugar ring position and use U instead of T. U is like T except without the methyl group. If I gave you a short length of polynucleotide and asked 'Is this RNA or DNA?' could you distinguish them? Point out purines (A, G) and pyrimidines (T/U, C). Only the N-bases distinguish positions in the polynucleotide chain chemically: Adenine, guanine; cytosine, thymine, uracil.

B. Figure 4-5, Lodish4e: Natural DNA is a right-handed double helix composed of complementary antiparallel chains. Explain the right-handed rule, with thumb pointing parallel to axis of symmetry and fingers curved in direction of helical twist.

C. Figure 1-10, Lodish5e: When Watson and Crick looked at their model for the structure of the double helix in 1953, it immediately suggested to them how DNA replicates. In each round of replication each of the two strands of DNA is used as a template for the formation of a complementary DNA strand. The original strands, but not the original double helix, remain intact through many cell generations.

Draw on board a short sequence of dsDNA and show how Chargaff's rules are used to make exact copies of the strands.

3. Figure 2-14, Lodish5e: All nucleotides have a common structure. a) Chemical structure of a representative nucleotide (ATP), a precursor to RNA since it has a 2' -OH group and is also the major energy carrier of cells. b) Structures of ribose (RNA) and deoxyribose (DNA), the pentose sugars in nucleic acids. The 2'-OH group in ribose makes RNA more reactive chemically than DNA, resulting for example in the hydrolysis of the phosphodiester bonds in RNA placed in basic or alkali solutions. The 2'-OH group is also involved in the enzymatic activity of certain RNA molecules called ribozymes.
Note to class: you will not be asked to draw from memory these and the other molecular structures that you encounter in this course, but be able to recognize them. There will be 25 chemical structures that you will need to recognize in this course: the 20 naturally occurring amino acids and the five nucleotide precursors of DNA and RNA (A, T, U, G and C).
 
4. Figure 2-15, Lodish5e: The chemical structures of the principal bases in nucleic acids. Know which ones are purines and which ones are pyrimidines, which ones are found in DNA and which ones in RNA, and be able to associate the structures of these N bases with their names.
 
5. Figure 4-2, Lodish5e: Alternative ways of representing nucleic acid chains using a single strand of DNA as an example. This figure is a particularly good example of the fact that the ends of the DNA molecule are chemically distinct and the meaning of the 5' to 3' directionality of the chain. RNA and DNA are synthesized in cells in the 5' to 3' direction and by convention, sequences are written left to right, 5' to 3', e.g. AUG is known to be (5')AUG(3') by this convention.
 
6. Table 2-2, Lodish5e: A good review of the naming conventions for nucleosides and nucleotides.
 

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