1. The structure of DNA

• DNA is a structure usually consisting of a right-handed helix made of two antiparallel strands, each made from the building blocks A, G (purines), T, and C (pyrimidines, along with U). (Purines have a double ring structure and pyrimidines have a single ring.) (fig. 2-17, Lodish) Ribose in DNA is 2-Deoxyribose. (fig. 2-16, Lodish)
• Strands of nucleic acids have 3' -> 5' directionality (fig. 4-2, Lodish)
• The two strands of DNA are held together by hydrogen bonds between complimentary bases. The exact match of hydrogen bonds reminds us of the specificity of bonding between enzyme and substrate! A space-filling model of the most common form of DNA, B-DNA, shows the sugar and phosphate groups forming the outline of the helix. The bases are found in grooves. (fig. 4-3, Lodish)
• Other forms of DNA, unknown to Watson and Crick, have been shown to exist. (fig. 4-4, Lodish). In 2005, "Nature" published a report on Z-DNA, a cover article. Please read the Nature report - you may be examined on its contents. (This link will take you right to the article on the Nature web site, IF you are connected to the UM network. If you are browsing from outside UM, a box will appear that requests your C-number and library pin number, as before.)
• Read about the reasons why DNA is more suitable for use as genetic material than RNA, pg. 118, and a discussion of base repair mechanisms on pg. 147, in detail. You will be examined on this material.

• DNA structure may be modified by binding of proteins, such as repressors. Look at this figure to see more about the TATA box-binding protein, TBP: (fig. 4-5, Lodish)

2. Information

• With four bases, we can code for 4 x 4 x 4 = 64 different amino acids, using a triplet code. Of course there are only about 20 amino acids, so there is some redundancy, and some codons (triplets) are used for start and stop signals, etc. (If we had only two bases, say A and T, how many different amino acids could triplets of these bases code for? With the same two bases, would we need groups of 4, 5, 6, or more to code for 20 different amino acids?)

3. Replication of DNA

• Replication of DNA is semiconservative. (fig. 4-29a, Lodish), (fig. 4-29b, Lodish)
• DNA replicates by parallel strands separating (remember that hydrogen bonds holding the strands together are weak and easily disrupted, particularly with help from an enzyme) and forming a replication fork. (fig. 4-30, Lodish) Notice that a short RNA primer must be used to begin synthesis of a DNA strand.
• Replication copies only from the 5' to 3' end of each strand. But, as a replication fork moves, it would seem that one strand would have to be made in a different direction than the other. A resolution of this problem was provided by the discovery of Okazaki fragments - One of the strands, the lagging strand, is synthesized discontinuously, and the fragments are then joined together. The other strand, the leading strand, is synthesized continuously. (fig. 4-31a, Lodish) The bidirectionality of replication is shown in: (fig. 4-33, Lodish)
• Read the discussion of the SV40 replication fork, pp. 141-143, in detail. You will be examined on this material.

4. Mistakes!

• DNA polymerase is a self-correcting enzyme which checks for the proper match of each base pair. If it finds an error, it slides backwards and corrects the mistake with 3'->5' exonuclease activity. The self-correction depends upon the fact that the chain grows from 5' to 3' with cleavage of two phosphates from the added nucleotide triphosphate. (fig. 4-34, Lodish)
• Errors can arise from modification or cross linking of nucleotide bases. Often this is the result of a change caused by chemical modification of the base or damage by X-rays, gamma rays, or UV light, all of which are energetic electromagnetic radiation. The conjugated double bonded ring structure of purines and pyrimidines is just the right dimension to absorb UV light strongly. (Some dyes with ring-shaped chromophores cause mutations. How do these dyes cause the mutation?) Cells can produce chemicals, particularly reactive oxygens that can cause point mutations, deamination of a cytosine base which is converted to uracil or conversion of a common 5-methylcytosine to a thymine: (fig. 4-35, Lodish)

All text and images, not attributed to others, including course examinations and sample questions, are Copyright, 2006, Thomas J. Herbert and may not be used for any commercial purpose without the express written permission of Thomas J. Herbert.