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Missense mutation
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=== Cellular mechanisms === [[DNA polymerase|DNA polymerases]], used in [[DNA replication]], have a high specificity of 10<sup>4</sup> to 10<sup>6</sup>-fold in base pairing.<ref name="Kunkel_2004" /> They have proofreading abilities to correct incorrect matches, allowing 90-99.9% of mismatches to be excised and repaired.<ref name="Kunkel_2004">{{cite journal | vauthors = Kunkel TA | title = DNA replication fidelity | journal = The Journal of Biological Chemistry | volume = 279 | issue = 17 | pages = 16895β16898 | date = April 2004 | pmid = 14988392 | doi = 10.1074/jbc.R400006200 | doi-access = free }}</ref> The base mismatches that go unnoticed are repaired by the DNA mismatch repair pathway, also inherent in cells.<ref name=":13">{{cite journal | vauthors = Li GM | title = Mechanisms and functions of DNA mismatch repair | journal = Cell Research | volume = 18 | issue = 1 | pages = 85β98 | date = January 2008 | pmid = 18157157 | doi = 10.1038/cr.2007.115 }}</ref><ref name=":14">{{cite journal | vauthors = Kunkel TA, Erie DA | title = DNA mismatch repair | journal = Annual Review of Biochemistry | volume = 74 | issue = 1 | pages = 681β710 | date = 2005-06-01 | pmid = 15952900 | doi = 10.1146/annurev.biochem.74.082803.133243 }}</ref> The DNA mismatch repair pathway uses [[Exonuclease|exonucleases]] that move along the DNA strand and remove the incorrectly incorporated base in order for DNA polymerase to fill in the correct base.<ref name=":13" />[[Exonuclease 1|Exonuclease1]] is involved in many DNA repair systems and moves 5' to 3' on the DNA strand.<ref>{{cite journal | vauthors = Goellner EM, Putnam CD, Kolodner RD | title = Exonuclease 1-dependent and independent mismatch repair | journal = DNA Repair | volume = 32 | pages = 24β32 | date = August 2015 | pmid = 25956862 | pmc = 4522362 | doi = 10.1016/j.dnarep.2015.04.010 }}</ref>
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