Editing Ribonucleotide (section)

==Function==

===Precursors of deoxyribonucleotides===
Scientists believe that RNA was developed before DNA.<ref>{{cite book |editor1-last=Chauhan |editor1-first=Ashok K. |editor2-last=Varma |editor2-first=Ajit |title=A textbook of molecular biotechnology |year=2009 |publisher=I.K. International Pub. House |location=New Delhi |isbn=978-93-80026-37-4}}</ref>

The reduction of ribonucleotides to deoxyribonucleotides is catalyzed by [[ribonucleotide reductase]]. Ribonucleotide reductase (RNR) is an essential enzyme for all living organisms since it is responsible for the last step in the synthesis of the four deoxyribonucleotides (dNTPs) necessary for DNA replication and repair.<ref>{{cite journal|last=Cendra Mdel|first=M|author2=Juárez, A |author3=Torrents, E |title=Biofilm modifies expression of ribonucleotide reductase genes in Escherichia coli.|journal=PLOS ONE|year=2012|volume=7|issue=9|pages=e46350|pmid=23050019|doi=10.1371/journal.pone.0046350|pmc=3458845|bibcode=2012PLoSO...746350C|doi-access=free}}</ref> The reaction also requires two other proteins: [[thioredoxin]] and [[thioredoxin reductase]]. Ribonucleoside diphosphate (NDP) is reduced by thioredoxin to a deoxyribonucleoside diphosphate (dNTP).

The general reaction is:<br/>
Ribonucleoside diphosphate + NADPH + {{chem2|H+ ->}} Deoxyribonucleoside diphosphate + {{chem2|NADP+}} + {{H2O}}
<ref>{{cite book |last1=Campbell |first1=Mary K. |last2=Farrell |first2=Shawn O. |title=Biochemistry |year=2009 |publisher=Brooks/Cole Cengage Learning |location=Belmont, CA |isbn=978-0-8400-6858-3 |edition=7th}}</ref>

To illustrate this equation, dATP and dGTP are synthesized from ADP and GDP, respectively. They are first reduced by RNR and then phosphorylated by nucleoside diphosphate kinases to dATP and dGTP. Ribonucleotide reductase is controlled by allosteric interactions. Once dATP binds to ribonucleotide reductase, the overall catalytic activity of the enzyme decreases, as it signifies an abundance of deoxyribonucleotides. This feedback inhibition is reversed once ATP binds.<ref name=Berg07/>

===Ribonucleotide discrimination===
During DNA synthesis, DNA polymerases must select against ribonucleotides, present at much higher levels compared with deoxyribonucleotides. It is crucial that there is selectivity as DNA replication has to be accurate to maintain the organism's genome. It has been shown that the active sites of Y-family DNA polymerases are responsible for maintaining a high selectivity against ribonucleotides.<ref>{{cite journal |last1=Kirouac |title=Structural Mechanism of Ribonucleotide Discrimination by a Y-Family DNA Polymerase|journal=Journal of Molecular Biology|date=1 April 2011|volume=407|issue=3|pages=382–390|doi=10.1016/j.jmb.2011.01.037|pmid=21295588|first1=Kevin N.|last2=Suo|first2=Zucai|last3=Ling|first3=Hong}}</ref> Most DNA polymerases are also equipped to exclude ribonucleotides from their active site through a bulky side chain residue that can sterically block the 2'-hydroxyl group of the ribose ring. However, many nuclear replicative and repair DNA polymerases incorporate ribonucleotides into DNA,<ref>{{cite journal |last1=Nick McElhinny |first1=SA |last2=Kumar |first2=D |last3=Clark |first3=AB |last4=Watt |first4=DL |last5=Watts |first5=BE |last6=Lundström |first6=EB |last7=Johansson |first7=E |last8=Chabes |first8=A |last9=Kunkel |first9=TA |title=Genome instability due to ribonucleotide incorporation into DNA. |journal=Nature Chemical Biology |date=October 2010 |volume=6 |issue=10 |pages=774–81 |doi=10.1038/nchembio.424 |pmid=20729855|pmc=2942972 }}</ref><ref>{{cite journal |last1=Nick McElhinny |first1=SA |last2=Watts |first2=BE |last3=Kumar |first3=D |last4=Watt |first4=DL |last5=Lundström |first5=EB |last6=Burgers |first6=PM |last7=Johansson |first7=E |last8=Chabes |first8=A |last9=Kunkel |first9=TA |title=Abundant ribonucleotide incorporation into DNA by yeast replicative polymerases. |journal=Proceedings of the National Academy of Sciences of the United States of America |date=16 March 2010 |volume=107 |issue=11 |pages=4949–54 |doi=10.1073/pnas.0914857107 |pmid=20194773|pmc=2841928 |bibcode=2010PNAS..107.4949N |doi-access=free }}</ref> suggesting that the exclusion mechanism is not perfect.<ref>{{cite journal|last=Kasiviswanathan|first=R|author2=Copeland, WC |title=Ribonucleotide discrimination and reverse transcription by the human mitochondrial DNA polymerase.|journal=The Journal of Biological Chemistry|date=Sep 9, 2011|volume=286|issue=36|pages=31490–500|pmid=21778232|doi=10.1074/jbc.M111.252460|pmc=3173122|doi-access=free}}</ref>