The Central Dogma of Molecular Biology

The sum total of all the DNA in an organism is called its genome. Genomic information is like a computer program for a cell. When you open a computer program, the program is copied from ROM (read‐only memory) on the hard disk to RAM (random‐access memory). The instructions in RAM are the ones that actually carry out the program, but the copy of the program in RAM exists only as long as there is power to the machine; if your PC loses power, you have to restart the program, and it is once again copied from the disk to RAM. This arrangement (hopefully) insures against the master copy of the program being damaged through a power surge or operator error.

If DNA is the master copy (the ROM) of a cell's genetic program, its integrity must be preserved. One way the DNA is protected is because RNA acts as the working copy (the RAM). Chemically, RNA is very similar to DNA. Biochemically, the major difference is that RNA either acts as a component of the metabolic machinery or is a copy of the information for protein synthesis. The relationship between DNA and RNA is called the central dogma of molecular biology:

DNA makes RNA makes protein

In the first of these processes, DNA sequences are transcribed into messenger RNA (mRNA). Messenger RNA is then translated to specify the sequence of the protein. DNA is replicated when each strand of DNA specifies the sequence of its partner to make two daughter molecules from one parental double‐stranded molecule.

DNA, RNA, and nucleotide structure

DNA is a polymer—a very large molecule made up of smaller units of four components. Each monomer contains a phosphate and a sugar component. In DNA, the sugar is deoxyribose, and in RNA the sugar is ribose.

and one of four bases, two of which are purines

and two of which are pyrimidines:

A sugar and a base make up a nucleoside. A base, sugar, and phosphate combine to form a nucleotide, as in thymidine monophosphate or adenosine monophosphate:

RNA is similar to DNA, although RNA nucleotides contain ribose rather than the deoxyribose found in DNA. Three bases found in DNA nucleotides are also found in RNA: adenine (A), guanine (G), and cytosine (C). Thymine in DNA is replaced by uracil in RNA:

DNA's duplex nature

DNA is normally double‐stranded. The sequences of the two strands are related so that an A on one strand is matched by a T on the other strand; likewise, a G on one strand is matched by a C on the other strand. Thus, the fraction of bases in an organism's DNA that are A is equal to the fraction of bases that are T, and the fraction of bases that are G is equal to the fraction of bases that are C. For example, if one‐third of the bases are A, one‐third must be T, and because the amount of G equals the amount of C, one‐sixth of the bases will be G and one‐sixth will be C. The importance of this relationship, termed Chargraff's rules, was recognized by Watson and Crick, who proposed that the two strands form a double helix with the two strands arranged in an antiparallel fashion, interwound head‐to‐tail, as Figure 1 shows.

Figure 1

You usually read nucleic acid sequences of DNA in a 5′ to 3′ direction, so a DNA dinucleotide of (5 ¹) adenosine‐guanosine (3 ¹) is read as AG.

The complementary sequence is CT, because both sequences are read in the 5′ to 3′ direction. The terms 5′ and 3′ refer to the numbers of the carbons on the sugar portion of the nucleotide (the base is attached to the 1′ carbon of the sugar).

Complementarity is determined by base pairing—the formation of hydrogen bonds between two complementary strands of DNA. An A–T base pair forms two H‐bonds, one between the amino group of A and the keto group of T and the second one between the ring nitrogen of A and the hydrogen on the ring nitrogen of T. A G–C base pair forms three H‐bonds, one between the amino group of C and the keto group of G, one between the ring nitrogen of C and the hydrogen on the ring nitrogen of G, and a third between the amino group of G and the keto group of C. DNA's double helix is a result of the two strands winding together, stabilized by the formation of H–bonds, and of the bases stacking on each other, as Figure 2 shows.

Figure 2

The DNA double helix and genetic replication

Because an A on one strand must base‐pair with a T on the other strand, if the two strands are separated, each single strand can specify the composition of its partner by acting as a template. The DNA template strand does not carry out any enzymatic reaction but simply allows the replication machinery (an enzyme) to synthesize the complementary strand correctly. This dual‐template mechanism is termed semi‐conservative, because each DNA after replication is composed of one parental and one newly synthesized strand. Because the two strands of the DNA double helix are interwound, they also must be separated by the replication machinery to allow synthesis of the new strand. Figure shows this replication.

Biochemistry I