A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds.
Dictated by specific hydrogen bonding patterns, "Watson–Crick" (or "Watson–Crick–Franklin") base pairs (guanine–cytosine and adenine–thymine)[1] allow the DNA helix to maintain a regular helical structure that is subtly dependent on its nucleotide sequence.
Crucially, however, stacking interactions are primarily responsible for stabilising the double-helical structure; Watson-Crick base pairing's contribution to global structural stability is minimal, but its role in the specificity underlying complementarity is, by contrast, of maximal importance as this underlies the template-dependent processes of the central dogma (e.g. DNA replication).
[12][citation needed] Mismatched base pairs can be generated by errors of DNA replication and as intermediates during homologous recombination.
The following abbreviations are commonly used to describe the length of a D/RNA molecule: For single-stranded DNA/RNA, units of nucleotides are used—abbreviated nt (or knt, Mnt, Gnt)—as they are not paired.
[15][16] An unnatural base pair (UBP) is a designed subunit (or nucleobase) of DNA which is created in a laboratory and does not occur in nature.
A few research groups have been searching for a third base pair for DNA, including teams led by Steven A. Benner, Philippe Marliere, Floyd E. Romesberg and Ichiro Hirao.
[18][19][20][21] In 1989 Steven Benner (then working at the Swiss Federal Institute of Technology in Zurich) and his team led with modified forms of cytosine and guanine into DNA molecules in vitro.
[23] In 2002, Ichiro Hirao's group in Japan developed an unnatural base pair between 2-amino-8-(2-thienyl)purine (s) and pyridine-2-one (y) that functions in transcription and translation, for the site-specific incorporation of non-standard amino acids into proteins.
[28] In 2012, a group of American scientists led by Floyd Romesberg, a chemical biologist at the Scripps Research Institute in San Diego, California, published that his team designed an unnatural base pair (UBP).
More technically, these artificial nucleotides bearing hydrophobic nucleobases, feature two fused aromatic rings that form a (d5SICS–dNaM) complex or base pair in DNA.
[29] In 2014 the same team from the Scripps Research Institute reported that they synthesized a stretch of circular DNA known as a plasmid containing natural T-A and C-G base pairs along with the best-performing UBP Romesberg's laboratory had designed and inserted it into cells of the common bacterium E. coli that successfully replicated the unnatural base pairs through multiple generations.
[17] The transfection did not hamper the growth of the E. coli cells and showed no sign of losing its unnatural base pairs to its natural DNA repair mechanisms.
[29][30] Romesberg said he and his colleagues created 300 variants to refine the design of nucleotides that would be stable enough and would be replicated as easily as the natural ones when the cells divide.
[31][32] In addition to the canonical pairing, some conditions can also favour base-pairing with alternative base orientation, and number and geometry of hydrogen bonds.
[37] In addition to these alternative base pairings, a wide range of base-base hydrogen bonding is observed in RNA secondary and tertiary structure.