Base-pairing and DNA Repair

Erwin Chargaff’s rules on DNA equivalence paved the way for the discovery of base pairing in DNA. Chargaff’s rules state that in a double-stranded DNA molecule,

1. the amount of adenine (A) is equal to the amount of thymine (T);
2. the amount of guanine (G) is equal to the amount of cytosine (C); and
3. the sum of purines, A and G, is equal to the sum of pyrimidines, C and T (i.e., A+G = C+T).

Later work by Watson and Crick revealed that in double-stranded DNA, A always forms two hydrogen bonds with T, and G always forms three hydrogen bonds with C.  This base pairing maintains a constant width of the DNA double helix, as both A-T and C-G pairs are 10.85Å in length and fit neatly between the two sugar-phosphate backbones.

Base pairings cause the nitrogenous bases to be inaccessible to other molecules until the hydrogen bonds separate. However, specific enzymes can easily break these hydrogen bonds to carry out necessary cell processes, such as DNA replication and transcription. As a G-C pair has more hydrogen bonds than an  A-T pair, DNA with a high percentage of G-C pairs will need the higher energy for separation of two strands of DNA than one with a similar percentage of A-T pairs. 

Base Analogs as Medicine

Correct base pairing is essential for the faithful replication of DNA. Base analogs are molecules that can replace the standard DNA bases during DNA replication. These analogs are effective antiviral and anticancer agents against diseases such as hepatitis, herpes, and leukemia. Acyclovir, also known as Acycloguanosine, is a base analog of guanine and is commonly used in the treatment of the herpes simplex virus.  The guanine part of Acyclovir pairs with adenine as usual during DNA replication; however, because it does not have a 3’ end of the nucleotide, DNA polymerase cannot continue forming base pairs, and replication terminates.