The term proofreading is used in genetics to refer to the error-correcting processes, first proposed by John Hopfield and Jacques Ninio, involved in DNA replication, immune system specificity, enzyme-substrate recognition among many other processes that require enhanced specificity. The proofreading mechanisms of Hopfield and Ninio are non-equilibrium active processes that consume ATP to enhance specificity of various biochemical reactions.
In bacteria, all three DNA polymerases (I, II and III) have the ability to proofread, using 3’ → 5’ exonuclease activity. When an incorrect base pair is recognized, DNA polymerase reverses its direction by one base pair of DNA and excises the mismatched base. Following base excision, the polymerase can re-insert the correct base and replication can continue.
In eukaryotes, only the polymerases that deal with the elongation (delta and epsilon) have proofreading ability (3’ → 5’ exonuclease activity).[1]
The extent of proofreading in DNA replication determines the mutation rate, and is different in different species.[4] For example, loss of proofreading due to mutations in the DNA polymerase epsilon gene results in a hyper-mutated genotype with >100 mutations per Mbase of DNA in human colorectal cancers.[5]
The extent of proofreading in other molecular processes can depend on the effective population size of the species and the number of genes affected by the same proofreading mechanism.[6]
Bacteriophage (phage) T4 gene 43 encodes the phage’s DNA polymerase replicative enzyme. Temperature-sensitive (ts) gene 43 mutants have been identified that have an antimutator phenotype, that is a lower rate of spontaneous mutation than wild type.[7] Studies of one of these mutants, tsB120, showed that the DNA polymerase specified by this mutant copies DNA templates at a slower rate than the wild-type polymerase.[8] However, the 3’ to 5’ exonuclease activity was no higher than wild-type. During DNA replication the ratio of nucleotides turned over to those stably incorporated into newly formed DNA is 10 to 100 times higher in the case of the tsB120 mutant than in wild-type.[8] It was proposed that the antimutator effect may be explained by both greater accuracy in nucleotide selection and an increased efficiency of removal of noncomplementary nucleotides (proofreading) by the tsB120 polymerase.
When phage T4 virions with a wild-type gene 43 DNA polymerase are exposed to either ultraviolet light, which introduces cyclobutane pyrimidine dimer damages in DNA, or psoralen-plus-light, which introduces pyrimidine adducts, the rate of mutation increases. However, these mutagenic effects are inhibited when the phage's DNA synthesis is catalyzed by the tsCB120 antimutator polymerase, or another antimutator polymerase, tsCB87.[9] These findings indicate that the level of induction of mutations by DNA damage can be strongly influenced by the gene 43 DNA polymerase proofreading function.
SARS-CoV-2 proofreading enzymeedit
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 pandemic. The SARS-CoV-2 RNA virus genome encodes a replication-and transcription complex, a multisubunit protein machine that carries out viral genome replication and transcription, processes essential to the virus life cycle. One of the proteins specified by the coronavirus genome is a non-structural protein, nsp14, that is a 3’-to-5’ exoribonuclease (ExoN). This protein resides in the protein complex nsp10-nsp14 that enhances replication fidelity by proofreading RNA synthesis, an activity critical for the virus life cycle.[10] Furthermore the coronavirus proofreading exoribonuclease nsp14-ExoN is required for maintaining genetic recombination generated during infection.[11]
Referencesedit
^Moldovan, G. L.; Pfander, B.; Jentsch, S. (2007). "PCNA, the Maestro of the Replication Fork". Cell. 129 (4): 665–79. doi:10.1016/j.cell.2007.05.003. PMID 17512402. S2CID 3547069.
^Pharmamotion --> Protein synthesis inhibitors: aminoglycosides mechanism of action animation. Classification of agents 2010-03-12 at the Wayback Machine Posted by Flavio Guzmán on 12/08/08
^Translation: Protein Synthesis by Joyce J. Diwan. Rensselaer Polytechnic Institute. Retrieved October 2011 2016-03-07 at the Wayback Machine
^Drake, J. W.; Charlesworth, B; Charlesworth, D; Crow, J. F. (1998). "Rates of spontaneous mutation". Genetics. 148 (4): 1667–86. doi:10.1093/genetics/148.4.1667. PMC1460098. PMID 9560386.
^Rajon, E., Masel, J.; Masel (2011). "Evolution of molecular error rates and the consequences for evolvability". PNAS. 108 (3): 1082–1087. Bibcode:2011PNAS..108.1082R. doi:10.1073/pnas.1012918108. PMC3024668. PMID 21199946.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^Drake JW, Allen EF. Antimutagenic DNA polymerases of bacteriophage T4. Cold Spring Harb Symp Quant Biol. 1968;33:339-44. doi: 10.1101/sqb.1968.033.01.039. PMID: 5254574.
^ abGillin FD, Nossal NG. Control of mutation frequency by bacteriophage T4 DNA polymerase. I. The CB120 antimutator DNA polymerase is defective in strand displacement. J Biol Chem. 1976 Sep 10;251(17):5219-24. PMID: 956182.
^Yarosh DB, Johns V, Mufti S, Bernstein C, Bernstein H. Inhibition of UV and psoralen-plus-light mutagenesis in phage T4 by gene 43 antimutator polymerase alleles. Photochem Photobiol. 1980 Apr;31(4):341-50. doi: 10.1111/j.1751-1097.1980.tb02551.x. PMID: 7384228.
^Liu C, Shi W, Becker ST, Schatz DG, Liu B, Yang Y. Structural basis of mismatch recognition by a SARS-CoV-2 proofreading enzyme. Science. 2021 Sep 3;373(6559):1142-1146. doi: 10.1126/science.abi9310. Epub 2021 Jul 27. PMID: 34315827
^Gribble J, Stevens LJ, Agostini ML, Anderson-Daniels J, Chappell JD, Lu X, Pruijssers AJ, Routh AL, Denison MR. The coronavirus proofreading exoribonuclease mediates extensive viral recombination. PLoS Pathog. 2021 Jan 19;17(1):e1009226. doi: 10.1371/journal.ppat.1009226. PMID: 33465137; PMCID: PMC7846108
External linksedit
Tseng, Shun-Fu; Gabriel, Abram; Teng, Shu-Chun (2008). "Proofreading Activity of DNA Polymerase Pol2 Mediates 3′-End Processing during Nonhomologous End Joining in Yeast". PLOS Genetics. 4 (4): e1000060. doi:10.1371/journal.pgen.1000060. PMC2312331. PMID 18437220.
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proofreading, biology, term, proofreading, used, genetics, refer, error, correcting, processes, first, proposed, john, hopfield, jacques, ninio, involved, replication, immune, system, specificity, enzyme, substrate, recognition, among, many, other, processes, . The term proofreading is used in genetics to refer to the error correcting processes first proposed by John Hopfield and Jacques Ninio involved in DNA replication immune system specificity enzyme substrate recognition among many other processes that require enhanced specificity The proofreading mechanisms of Hopfield and Ninio are non equilibrium active processes that consume ATP to enhance specificity of various biochemical reactions In bacteria all three DNA polymerases I II and III have the ability to proofread using 3 5 exonuclease activity When an incorrect base pair is recognized DNA polymerase reverses its direction by one base pair of DNA and excises the mismatched base Following base excision the polymerase can re insert the correct base and replication can continue In eukaryotes only the polymerases that deal with the elongation delta and epsilon have proofreading ability 3 5 exonuclease activity 1 Proofreading also occurs in mRNA translation for protein synthesis 2 In this case one mechanism is the release of any incorrect aminoacyl tRNA before peptide bond formation 3 The extent of proofreading in DNA replication determines the mutation rate and is different in different species 4 For example loss of proofreading due to mutations in the DNA polymerase epsilon gene results in a hyper mutated genotype with gt 100 mutations per Mbase of DNA in human colorectal cancers 5 The extent of proofreading in other molecular processes can depend on the effective population size of the species and the number of genes affected by the same proofreading mechanism 6 Contents 1 Bacteriophage T4 DNA polymerase 2 SARS CoV 2 proofreading enzyme 3 References 4 External linksBacteriophage T4 DNA polymerase editBacteriophage phage T4 gene 43 encodes the phage s DNA polymerase replicative enzyme Temperature sensitive ts gene 43 mutants have been identified that have an antimutator phenotype that is a lower rate of spontaneous mutation than wild type 7 Studies of one of these mutants tsB120 showed that the DNA polymerase specified by this mutant copies DNA templates at a slower rate than the wild type polymerase 8 However the 3 to 5 exonuclease activity was no higher than wild type During DNA replication the ratio of nucleotides turned over to those stably incorporated into newly formed DNA is 10 to 100 times higher in the case of the tsB120 mutant than in wild type 8 It was proposed that the antimutator effect may be explained by both greater accuracy in nucleotide selection and an increased efficiency of removal of noncomplementary nucleotides proofreading by the tsB120 polymerase When phage T4 virions with a wild type gene 43 DNA polymerase are exposed to either ultraviolet light which introduces cyclobutane pyrimidine dimer damages in DNA or psoralen plus light which introduces pyrimidine adducts the rate of mutation increases However these mutagenic effects are inhibited when the phage s DNA synthesis is catalyzed by the tsCB120 antimutator polymerase or another antimutator polymerase tsCB87 9 These findings indicate that the level of induction of mutations by DNA damage can be strongly influenced by the gene 43 DNA polymerase proofreading function SARS CoV 2 proofreading enzyme editSevere acute respiratory syndrome coronavirus 2 SARS CoV 2 is the causative agent of the COVID 19 pandemic The SARS CoV 2 RNA virus genome encodes a replication and transcription complex a multisubunit protein machine that carries out viral genome replication and transcription processes essential to the virus life cycle One of the proteins specified by the coronavirus genome is a non structural protein nsp14 that is a 3 to 5 exoribonuclease ExoN This protein resides in the protein complex nsp10 nsp14 that enhances replication fidelity by proofreading RNA synthesis an activity critical for the virus life cycle 10 Furthermore the coronavirus proofreading exoribonuclease nsp14 ExoN is required for maintaining genetic recombination generated during infection 11 References edit Moldovan G L Pfander B Jentsch S 2007 PCNA the Maestro of the Replication Fork Cell 129 4 665 79 doi 10 1016 j cell 2007 05 003 PMID 17512402 S2CID 3547069 Pharmamotion gt Protein synthesis inhibitors aminoglycosides mechanism of action animation Classification of agents Archived 2010 03 12 at the Wayback Machine Posted by Flavio Guzman on 12 08 08 Translation Protein Synthesis by Joyce J Diwan Rensselaer Polytechnic Institute Retrieved October 2011 Archived 2016 03 07 at the Wayback Machine Drake J W Charlesworth B Charlesworth D Crow J F 1998 Rates of spontaneous mutation Genetics 148 4 1667 86 doi 10 1093 genetics 148 4 1667 PMC 1460098 PMID 9560386 The Cancer Genome Atlas Network Bainbridge Chang Dinh Drummond Fowler Kovar Lewis Morgan Newsham Reid Santibanez Shinbrot Trevino Wu Wang Gunaratne Donehower Creighton Wheeler Gibbs Lawrence Voet Jing Cibulskis Sivachenko Stojanov McKenna Lander et al 2012 Comprehensive molecular characterization of human colon and rectal cancer Nature 487 7407 330 337 Bibcode 2012Natur 487 330T doi 10 1038 nature11252 PMC 3401966 PMID 22810696 Rajon E Masel J Masel 2011 Evolution of molecular error rates and the consequences for evolvability PNAS 108 3 1082 1087 Bibcode 2011PNAS 108 1082R doi 10 1073 pnas 1012918108 PMC 3024668 PMID 21199946 a href Template Cite journal html title Template Cite journal cite journal a CS1 maint multiple names authors list link Drake JW Allen EF Antimutagenic DNA polymerases of bacteriophage T4 Cold Spring Harb Symp Quant Biol 1968 33 339 44 doi 10 1101 sqb 1968 033 01 039 PMID 5254574 a b Gillin FD Nossal NG Control of mutation frequency by bacteriophage T4 DNA polymerase I The CB120 antimutator DNA polymerase is defective in strand displacement J Biol Chem 1976 Sep 10 251 17 5219 24 PMID 956182 Yarosh DB Johns V Mufti S Bernstein C Bernstein H Inhibition of UV and psoralen plus light mutagenesis in phage T4 by gene 43 antimutator polymerase alleles Photochem Photobiol 1980 Apr 31 4 341 50 doi 10 1111 j 1751 1097 1980 tb02551 x PMID 7384228 Liu C Shi W Becker ST Schatz DG Liu B Yang Y Structural basis of mismatch recognition by a SARS CoV 2 proofreading enzyme Science 2021 Sep 3 373 6559 1142 1146 doi 10 1126 science abi9310 Epub 2021 Jul 27 PMID 34315827 Gribble J Stevens LJ Agostini ML Anderson Daniels J Chappell JD Lu X Pruijssers AJ Routh AL Denison MR The coronavirus proofreading exoribonuclease mediates extensive viral recombination PLoS Pathog 2021 Jan 19 17 1 e1009226 doi 10 1371 journal ppat 1009226 PMID 33465137 PMCID PMC7846108External links editIdaho U DNA proofreading and repair DNA polymerase e and d proofreading suppress discrete mutator and cancer phenotypes in mice Tseng Shun Fu Gabriel Abram Teng Shu Chun 2008 Proofreading Activity of DNA Polymerase Pol2 Mediates 3 End Processing during Nonhomologous End Joining in Yeast PLOS Genetics 4 4 e1000060 doi 10 1371 journal pgen 1000060 PMC 2312331 PMID 18437220 nbsp This genetics article is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title Proofreading biology amp oldid 1188165691, wikipedia, wiki, book, books, library,
