DNA INVERTED REPEATS AND HUMAN DISEASE

John J. Bissler

The Children's Hospital Research Foundation, Cincinnati, Ohio

3. INVERTED REPEATS

The human genome is far from random and has a number of repeat sequence types. The easiest to understand is the direct repeat in which the sequence is duplicated (figure 1A). The arrows over the sequence indicate the sequence that is repeated. Linguistically, an example of a direct repeat is "bye-bye". An inverted repeat, also called a palindrome, is similar except the second half of the repeat is in the complementary strand (figure 1B). A palindrome linguistically is a string of characters that reads the same in both directions, such as "noon". A consequence of these repeats being inverted is that they can base pair to the complementary strands through intermolecular base pairing, or to themselves through intramolecular base pairing. In Figure 1B, the black vertical lines represent the intermolecular base pairing and the gray concentric circles illustrate the potential intramolecular base pairing. Practically speaking, single-stranded DNA cannot bend sharply enough so that adjacent nucleotides on one strand can hydrogen bond as base pairs. There is a mandatory 3-5 bp spacer or loop between the 5' and 3' stems that allow the DNA to fold back on itself. In figure 2A, a single-stranded inverted repeat is written as a hairpin, however this is far from reality, and figure 2B illustrates the twist of the DNA. The crystallized hairpin structure is illustrated in Figure 2C (8). These stem-loop structures can form in single-stranded DNA and are called "hairpins", or can form in both strands of the duplex DNA and are called "cruciforms". The terms inverted repeat and palindrome imply a perfect nature to the sequence. Sequences that are not perfect are called imperfect inverted repeats or quasipalindromes.

Figure 1: Direct and inverted DNA repeats. A. Direct repeats are illustrated with an arrow above the sequence that is repeated. Dark vertical bars represent interstand binding between complementary strands. B. Inverted repeats are illustrated with the opposing arrows above the sequence. The vertical line perpendicular to the sequence denoted the center of the inverted repeat. Black vertical lines represents interstrand binding between complementary strands, while the gray concentric lines denote the intrastrand complementary nature of the bases in the inverted repeat.

Figure 2: Inverted repeats can form hairpin structures. A. An inverted repeat drawn as a hairpin structure. This can occur in both strands of complementary DNA forming a cruciform structure. B. A more realistic illustration of the hairpin structure illustrating the twist. Gray letters indicate the sequence is behind the overlying black sequence. C. Crystal structure of the inverted repeat plotted using RasMac Molecular Graphic Macintosh Version 2.6 and clearly shows the unpaired loop at the top of the hairpin structure.