If you ask any biologist for a definition for base pairing, you’ll get a very similar explanation. Base pairing is the association between two nucleobases on opposite ends of a DNA or RNA molecule.

The two nucleobases are held together by hydrogen bonds, which form between a hydrogen atom on one base (purines) and an oxygen or nitrogen atom on the other base (pyrimidines).

The bases on one strand of DNA always match with the opposite strand of DNA. There are four different kinds of base pairing, A-T, T-A, G-C and C-G. This is in accordance with the accepted stereochemical model for DNA double-helical structure. The B-DNA model, assumes that each strand is a regular helix containing nucleotides that are chemically and structurally identical.

However, the hydrogen bond is relatively weak and can be easily broken.

When this happens, sometimes a new form of base pairing occur. This base pairing is against the conventional Watson and Crick model.

Hoogsteen (HG) base pairs (bps) were discovered in 1959 when Karst Hoogsteen used single crystal X-ray crystallography to visualize the pairing between 1-methylthymine and 9-methyladenine.


Hogsteen base pairing in DNA


Hogsteen DNA base pairing
Hogsteen DNA model

Hogsteen base pairing (HG bps) develop in duplex DNA by rotating the purine base 180° around the glycosidic bond, causing the purine base to assume a syn rather than anti conformation.

In addition, H-bonds requires that the two bases come into closer proximity, thus constricting the C1′–C1′ distance by ∼2 Å relative to Watson Crick of 2.4 Å

During A-T base pairing with a double bond, they retain the Adenine N6–H–O4-Thymine Hydrogen bond. However, the other bond Adenines’ N1–H–N3 Thymine is replaced by Adenine N7–H–N3 bond.

Due to change in N7 position of the purine, which is base-paired in Hoogsteen base pairing, changes the chemical reactivity of this location.


Hogsteen base pairing in RNA

Hogsteen base pairing is the structure of double helical RNA molecule. The acceptor stem contains a uridine at the 5’th position which pairs with the 5’th position of the 5-C/U substrate on the complementary strand of the helical RNA molecule.

This is a result of the fact that the 5′ hydroxy group of uridine on the acceptor stem can form hydrogen bonds with the 4′ carbon of the adjacent 3′ C/U on the complementary strand.  The donor stem is made up of the complementary base, cytosine, at the 5’th position and a uridine at the 3’rd position.

The 5’th position of the cytosine on the donor strand is a part of the acceptance stem and the 3’rd uridine on the same strand is a part of donor stem, hence the name ‘Hogsteen base pairing’.

Roles of Hogsteen Base pairing in DNA

The hogsteen base pairing system carry out some crucial functions in the cell.

  • HG bps help avoid a steric clash between the guanine exocyclic NH2 group and a nearby leucine side chain of the TATA box-binding protein (TBP).
  • Hogsteen base pairing have also been observed in chemically modified DNA, including N2-propanoguanine and 8-amino-purine where they may contribute to damage accommodation, recognition and repair of the DNA.