phosphodiester bonds

Meaning: A phosphodiester bond is a phosphate group esterified to two sugar hydroxyls: the 3′ OH of one nucleotide and the 5′ phosphate of the next. Repeating the link gives the sugar-phosphate backbone, which has direction (5′ end to 3′ end). Polymerases build the chain by adding a nucleoside triphosphate to the 3′ OH and releasing pyrophosphate. Hydrolysis of that pyrophosphate helps drive the reaction forward. Each backbone phosphate is negatively charged at physiological pH, so nucleic acids are acidic and bind positively charged proteins such as histones.

On the MCAT: Expect questions on which enzymes make or break these bonds. DNA polymerase, RNA polymerase and DNA ligase form them (ligase seals nicks, such as between Okazaki fragments). Nucleases and restriction enzymes hydrolyze them. You may be asked to find the 5′ and 3′ ends of a drawn strand, or to explain why RNA is hydrolyzed more easily than DNA (its 2′ OH can attack the neighboring phosphate). Melting or heating a duplex is another common setup.

Common confusion: Students mix up the bonds that hold the strand together with the bonds that hold the two strands together. Phosphodiester bonds are covalent and run along each strand. Hydrogen bonds pair the bases across strands. Denaturation breaks the hydrogen bonds only. Also, do not confuse these with the phosphoanhydride bonds of ATP.