Nucleotide base

{{Short description|Nitrogen-containing biological compounds that form nucleosides}} {{Redirect|ACGT|the Japanese animation production company|A.C.G.T}} {{Use dmy dates|date=June 2021}} [[File:AGCT RNA mini.svg|thumb|350px|Base pairing: two base pairs are produced by four nucleotide monomers, nucleobases are in blue. Guanine (G) is paired with cytosine (C) via three hydrogen bonds, in red. Adenine (A) is paired with uracil (U) via two hydrogen bonds, in red.]]

'''Nucleotide bases'''<ref>{{Cite journal|title=IUPAC - nucleotide bases (N04254)|last=The International Union of Pure and Applied Chemistry (IUPAC)|doi=10.1351/goldbook.N04254 |doi-access=free}}</ref> (also '''nucleobases''', '''nitrogenous bases''') are nitrogen-containing biological compounds that form nucleosides, which, in turn, are components of nucleotides, with all of these monomers constituting the basic building blocks of nucleic acids. The ability of nucleobases to form base pairs and to stack one upon another leads directly to long-chain helical structures such as deoxyribonucleic acid (DNA). Five nucleobases—adenine (A), cytosine (C), guanine (G), thymine (T), and uracil (U)—are called ''primary'' or ''canonical''. They function as the fundamental units of the genetic code, with the bases A, C, G and T being found in DNA while A, C, G and U are found in RNA. Thymine and uracil are distinguished by merely the presence or absence of a methyl group on the fifth carbon (C5) of these heterocyclic six-membered rings.<ref>{{cite book|last=Soukup|first=Garrett A.|title=eLS|date=2003|chapter=Nucleic Acids: General Properties|publisher=American Cancer Society|language=en|doi=10.1038/npg.els.0001335|isbn=9780470015902}}</ref>{{page needed|date=January 2021}} In addition, some viruses have aminoadenine (Z) instead of adenine. It differs in having an extra amine group, creating a more stable bond to thymine.<ref>{{Cite web|url=https://www.sciencenews.org/article/virus-dna-z-bacteriophage-genetic-alphabet-bond-life|title=Some viruses thwart bacterial defenses with a unique genetic alphabet|date=5 May 2021}}</ref>

{{multiple image | image1 = Blausen 0323 DNA Purines.png | caption1 = Purine nucleobases are fused-ring molecules.

| image2 = Blausen 0324 DNA Pyrimidines.png | caption2 = Pyrimidine nucleobases are simple ring molecules. }}

Adenine and guanine have a fused-ring skeletal structure derived of purine, hence they are called '''purine bases'''.<ref>{{Cite journal|url=https://goldbook.iupac.org/terms/view/P04953|title=IUPAC - purine bases (P04953)|last=The International Union of Pure and Applied Chemistry (IUPAC)|website=goldbook.iupac.org|doi=10.1351/goldbook.p04953|doi-access=free|url-access=subscription}}</ref> The purine nitrogenous bases are characterized by their single amino group ({{chem2|\sNH2}}), at the C6 carbon in adenine and C2 in guanine.<ref name="NIH.gov">{{cite journal | vauthors = Berg JM, Tymoczko JL, Stryer L | title = Section 25.2, Purine Bases Can Be Synthesized de Novo or Recycled by Salvage Pathways. | journal = Biochemistry. 5th Edition | url = https://www.ncbi.nlm.nih.gov/books/NBK22385/| archive-url = https://web.archive.org/web/20190104182440/https://www.ncbi.nlm.nih.gov/books/NBK22385/| url-status = dead| archive-date = 4 January 2019| access-date = 2019-12-11 }}</ref> Similarly, the simple-ring structure of cytosine, uracil, and thymine is derived of pyrimidine, so those three bases are called the '''pyrimidine bases'''.<ref>{{Cite journal|url=https://goldbook.iupac.org/terms/view/P04958|title=IUPAC - pyrimidine bases (P04958)|last=The International Union of Pure and Applied Chemistry (IUPAC)|website=goldbook.iupac.org|doi=10.1351/goldbook.p04958|doi-access=free|url-access=subscription}}</ref>

Each of the base pairs in a typical double-helix DNA comprises a purine and a pyrimidine: either an A paired with a T or a C paired with a G. These purine-pyrimidine pairs, which are called ''base complements'', connect the two strands of the helix and are often compared to the rungs of a ladder. Only pairing purine with pyrimidine ensures a constant width for the DNA. The A–T pairing is based on two hydrogen bonds, while the C–G pairing is based on three. In both cases, the hydrogen bonds are between the amine and carbonyl groups on the complementary bases.

Nucleobases such as adenine, guanine, xanthine, hypoxanthine, purine, 2,6-diaminopurine, and 6,8-diaminopurine may have formed in outer space as well as on earth.<ref name="Callahan">{{cite journal | vauthors = Callahan MP, Smith KE, Cleaves HJ, Ruzicka J, Stern JC, Glavin DP, House CH, Dworkin JP | title = Carbonaceous meteorites contain a wide range of extraterrestrial nucleobases | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 34 | pages = 13995–8 | date = August 2011 | pmid = 21836052 | pmc = 3161613 | doi = 10.1073/pnas.1106493108 | publisher = PNAS | bibcode = 2011PNAS..10813995C | doi-access = free }}</ref><ref name="Steigerwald">{{cite web |last=Steigerwald |first=John |title=NASA Researchers: DNA Building Blocks Can Be Made in Space |url=http://www.nasa.gov/topics/solarsystem/features/dna-meteorites.html |publisher=NASA |date=8 August 2011 |access-date=2011-08-10 |archive-date=11 May 2020 |archive-url=https://web.archive.org/web/20200511192941/https://www.nasa.gov/topics/solarsystem/features/dna-meteorites.html |url-status=dead }}</ref><ref name="DNA">{{cite web |author=ScienceDaily Staff |title=DNA Building Blocks Can Be Made in Space, NASA Evidence Suggests |url=https://www.sciencedaily.com/releases/2011/08/110808220659.htm |date=9 August 2011 |website=ScienceDaily |access-date=2011-08-09}}</ref>

The origin of the term ''base'' reflects these compounds' chemical properties in acid–base reactions, but those properties are not especially important for understanding most of the biological functions of nucleobases.

==Structure== [[File:DNA chemical structure.svg|thumb|350px|Chemical structure of DNA, showing four nucleobase pairs produced by eight nucleotides: adenine (A) is joined to thymine (T), and guanine (G) is joined to cytosine (C). + This structure also shows the directionality of each of the two phosphate-deoxyribose backbones, or strands. The 5' to 3' (''read'' "5 prime to 3 prime") directions are: ''down'' the strand on the left, and ''up'' the strand on the right. The strands twist around each other to form a double helix structure.]]

At the sides of nucleic acid structure, phosphate molecules successively connect the two sugar-rings of two adjacent nucleotide monomers, thereby creating a long chain biomolecule. These chain-joins of phosphates with sugars (ribose or deoxyribose) create the "backbone" strands for a single- or double helix biomolecule.

In the double helix of DNA, the two strands are oriented chemically in opposite directions, which permits base pairing by providing complementarity between the two bases, and which is essential for replication of or transcription of the encoded information found in DNA.{{citation needed|date=May 2024}}

==Modified nucleobases== DNA and RNA also contain other (non-primary) bases that have been modified after the nucleic acid chain has been formed. In DNA, the most common modified base is 5-methylcytosine (m5C). In RNA, there are many modified bases, including those contained in the nucleosides pseudouridine (Ψ), dihydrouridine (D), inosine (I), and 7-methylguanosine (m7G).<ref>{{cite web |last1=Stavely |first1=Brian E. |title=BIOL2060: Translation |url=https://www.mun.ca/biology/desmid/brian/BIOL2060/BIOL2060-22/CB22.html |website=www.mun.ca |access-date=17 August 2020}}</ref><ref>[http://www.biogeo.uw.edu.pl/research/grupaC_en.html "Role of 5' mRNA and 5' U snRNA cap structures in regulation of gene expression"] – Research – Retrieved 13 December 2010.</ref>

Hypoxanthine and xanthine are two of the many bases created through mutagen presence, both of them through deamination (replacement of the amine-group with a carbonyl-group). Hypoxanthine is produced from adenine, xanthine from guanine,<ref name="pmid1557408">{{cite journal | vauthors = Nguyen T, Brunson D, Crespi CL, Penman BW, Wishnok JS, Tannenbaum SR | title = DNA damage and mutation in human cells exposed to nitric oxide in vitro | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 89 | issue = 7 | pages = 3030–4 | date = April 1992 | pmid = 1557408 | pmc = 48797 | doi = 10.1073/pnas.89.7.3030 | bibcode = 1992PNAS...89.3030N | doi-access = free }}</ref> and uracil results from deamination of cytosine.

=== Examples of modified nucleobases ===

{| class="wikitable sortable skin-invert-image" style="text-align:center" |+Modified purine nucleobases (mostly modified A or G) |- valign="bottom" ! valign=middle scope=row rowspan=2|Nucleobase | 70px|Chemical structure of hypoxanthine || 75px|Chemical structure of xanthine || 93px|Chemical structure of 7-methylguanine || 70px|Chemical structure of 9H-purine |- |Hypoxanthine|| Xanthine|| 7-Methylguanine || 9H-purine |- valign="bottom" ! valign=middle scope=row rowspan=2|Nucleoside | 95px|Chemical structure of inosine || 105px|Chemical structure of xanthosine || 140px|Chemical structure of 7-methylguanosine || 120px|Chemical structure of nebularine |- || Inosine || Xanthosine || 7-Methylguanosine || Nebularine |- ! scope=row | Short symbol | I || X || m7G || P<ref>{{cite journal |last1=Jolley |first1=EA |last2=Znosko |first2=BM |title=The loss of a hydrogen bond: Thermodynamic contributions of a non-standard nucleotide |journal=Nucleic Acids Research |date=2016 |volume=45 |issue=3 |pages=1479–1487 |doi=10.1093/nar/gkw830 |pmid=28180321 |pmc=5388425}}</ref> |}

{| class="wikitable skin-invert-image" style="text-align:center" |+Modified pyrimidine nucleobases (modified C, U, or T) |- valign="bottom" ! valign=middle scope=row rowspan=2|Nucleobase | 55px|Chemical structure of dihydrouracil || 75px|Chemical structure of 5-methylcytosine || 60px|Chemical structure of 5-hydroxymethylcytosine |- |5,6-Dihydrouracil|| 5-Methylcytosine|| 5-Hydroxymethylcytosine |- valign="bottom" ! valign=middle scope=row rowspan=2|Nucleoside | 87px|Chemical structure of dihydrouridine || 87px|Chemical structure of 5-methylcytidine || 87px |- || Dihydrouridine || 5-Methylcytidine || Pseudouridine |- ! scope=row | Short symbol | D, hU<ref name=iupac70>{{Cite journal | author = IUPAC-IUB Commission on Biochemical Nomenclature | doi = 10.1021/bi00822a023 | title = Abbreviations and symbols for nucleic acids, polynucleotides, and their constituents | journal = Biochemistry | volume = 9 | issue = 20 | pages = 4022–4027 | year = 1970|url=https://iupac.qmul.ac.uk/misc/naabb.html#p44 }}</ref>{{rp|N3.2.1, N4.1}} || m5C || Ψ |}

A list of modified bases and their symbols can be found in the many nucleic acid modification databases and as part of tRNAdb.<ref>{{cite web |title=ABBREVIATION OF MODIFIED BASES |url=http://trnadb.bioinf.uni-leipzig.de/DataOutput/images/mod.pdf|archive-url=https://web.archive.org/web/20230922110911/http://trnadb.bioinf.uni-leipzig.de/DataOutput/images/mod.pdf |archive-date=22 September 2023 }}</ref>

==Artificial nucleobases== {{Main|Nucleic acid analogue}} A vast number of nucleobase analogues exist. The most common applications are used as fluorescent probes, either directly or indirectly, such as aminoallyl nucleotide, which are used to label cRNA or cDNA in microarrays. Several groups are working on alternative "extra" base pairs to extend the genetic code, such as isoguanine and isocytosine or the fluorescent 2-amino-6-(2-thienyl)purine and pyrrole-2-carbaldehyde.<ref name="pmid15051811">{{cite journal|vauthors=Johnson SC, Sherrill CB, Marshall DJ, Moser MJ, Prudent JR|date=2004|title=A third base pair for the polymerase chain reaction: inserting isoC and isoG|journal=Nucleic Acids Research|volume=32|issue=6|pages=1937–41|doi=10.1093/nar/gkh522|pmc=390373|pmid=15051811}}</ref><ref>{{cite journal|vauthors=Kimoto M, Mitsui T, Harada Y, Sato A, Yokoyama S, Hirao I|year=2007|title=Fluorescent probing for RNA molecules by an unnatural base-pair system|journal=Nucleic Acids Research|volume=35|issue=16|pages=5360–69|doi=10.1093/nar/gkm508|pmc=2018647|pmid=17693436}}</ref>

In medicine, several nucleoside analogues are used as anticancer and antiviral agents. The viral polymerase incorporates these compounds with non-canonical bases. These compounds are activated in the cells by being converted into nucleotides; they are administered as nucleosides as charged nucleotides cannot easily cross cell membranes.{{Citation needed|date=April 2012}} At least one set of new base pairs has been announced as of May 2014.<ref>{{cite journal | vauthors = Malyshev DA, Dhami K, Lavergne T, Chen T, Dai N, Foster JM, Corrêa IR, Romesberg FE | title = A semi-synthetic organism with an expanded genetic alphabet | journal = Nature | volume = 509 | issue = 7500 | pages = 385–8 | date = May 2014 | pmid = 24805238 | pmc = 4058825 | doi = 10.1038/nature13314 | bibcode = 2014Natur.509..385M }}</ref>

==Prebiotic condensation of nucleobases with ribose==

In order to understand how life arose, knowledge is required of chemical pathways that permit formation of the key building blocks of life under plausible prebiotic conditions. According to the RNA world hypothesis, free-floating ribonucleotides were present in the primordial soup. These were the fundamental molecules that combined in series to form RNA. Molecules as complex as RNA must have arisen from small molecules whose reactivity was governed by physico-chemical processes. RNA is composed of purine and pyrimidine nucleotides, both of which are necessary for reliable information transfer, and thus Darwinian evolution. Nam et al.<ref>{{Cite journal |doi=10.1073/pnas.1718559115 |pmc=5776833 |pmid=29255025 |doi-access=free|title=Abiotic synthesis of purine and pyrimidine ribonucleosides in aqueous microdroplets |year=2018 |last1=Nam |first1=Inho |last2=Nam |first2=Hong Gil |last3=Zare |first3=Richard N. |journal=Proceedings of the National Academy of Sciences |volume=115 |issue=1 |pages=36–40 |bibcode=2018PNAS..115...36N }}</ref> demonstrated the direct condensation of nucleobases with ribose to give ribonucleosides in aqueous microdroplets, a key step leading to RNA formation. Similar results were obtained by Becker et al.<ref>{{Cite journal |doi=10.1126/science.aax2747 |pmid=31604305|title=Unified prebiotically plausible synthesis of pyrimidine and purine RNA ribonucleotides |year=2019 |last1=Becker |first1=Sidney |last2=Feldmann |first2=Jonas |last3=Wiedemann |first3=Stefan |last4=Okamura |first4=Hidenori |last5=Schneider |first5=Christina |last6=Iwan |first6=Katharina |last7=Crisp |first7=Antony |last8=Rossa |first8=Martin |last9=Amatov |first9=Tynchtyk |last10=Carell |first10=Thomas |journal=Science |volume=366 |issue=6461 |pages=76–82 |bibcode=2019Sci...366...76B |s2cid=203719976 |url=https://epub.ub.uni-muenchen.de/71503/1/Science_Becker_2019.pdf }}</ref>

== See also == * {{annotated link|Nucleoside}} * {{annotated link|Nucleotide}} * {{annotated link|Nucleic acid notation}} * {{annotated link|Nucleic acid sequence}}

== References == {{Reflist}}

== External links == * [https://web.archive.org/web/20060621234655/http://www.elmhurst.edu/~chm/vchembook/582dnadoublehelix.html Base pairing in DNA Double Helix (shows specific hydrogen bonds)]

Category:Nucleobases Category:DNA Category:RNA