241:. If left uncorrected, these adducts, after misreplication past the damaged sites, can give rise to mutations. In nature, the mutations that arise may be beneficial or deleterious—this is the driving force of evolution. An organism may acquire new traits through genetic mutation, but mutation may also result in impaired function of the genes and, in severe cases, causes the death of the organism. Mutation is also a major source for acquisition of
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be examined in detail. The mutation may also produce mutant proteins with altered properties, or enhanced or novel functions that may prove to be of use commercially. Mutant strains of organisms that have practical applications, or allow the molecular basis of particular cell function to be investigated, may also be produced.
221:). The incorrect insertion in the new strand will occur opposite the damaged site in the template strand, and this incorrect insertion can become a mutation (i.e. a changed base pair) in the next round of replication. Furthermore, double-strand breaks in DNA may be repaired by an inaccurate repair process,
273:
Mutagenesis may also be self-induced by unicellular organisms when environmental conditions are restrictive to the organism's growth, such as bacteria growing in the presence of antibiotics, yeast growing in the presence of an antifungal agent, or other unicellular organisms growing in an environment
245:
in bacteria, and to antifungal agents in yeasts and molds. In a laboratory setting, mutagenesis is a useful technique for generating mutations that allows the functions of genes and gene products to be examined in detail, producing proteins with improved characteristics or novel functions, as well as
229:
systems recognize DNA damage and repair it prior to completion of the next round of replication. At least 169 enzymes are either directly employed in DNA repair or influence DNA repair processes. Of these, 83 are directly employed in the 5 types of DNA repair processes indicated in the chart shown in
175:
While changes to the chromosome caused by X-ray and mustard gas were readily observable to early researchers, other changes to the DNA induced by other mutagens were not so easily observable; the mechanism by which they occur may be complex, and take longer to unravel. For example, soot was suggested
749:
In the laboratory, mutagenesis is a technique by which DNA mutations are deliberately engineered to produce mutant genes, proteins, or strains of organisms. Various constituents of a gene, such as its control elements and its gene product, may be mutated so that the function of a gene or protein can
429:
is a related process in which the histone proteins around which DNA coils can be similarly modified via methylation, phosphorylation, or acetylation; these modifications may act to alter gene expression of the local DNA, and may also act to denote locations of damaged DNA in need of repair. DNA may
457:
catalyzed by cytochrome P450. These metabolites form adducts with the DNA, which can cause errors in replication, and the bulky aromatic adducts may form stable intercalation between bases and block replication. The adducts may also induce conformational changes in the DNA. Some adducts may also
702:
Adaptive mutagenesis has been defined as mutagenesis mechanisms that enable an organism to adapt to an environmental stress. Since the variety of environmental stresses is very broad, the mechanisms that enable it are also quite broad, as far as research on the field has shown. For instance, in
1602:
Kong, A.; Frigge, M. L.; Masson, G.; Besenbacher, S.; Sulem, P.; Magnusson, G.; Gudjonsson, S. A.; Sigurdsson, A.; Jonasdottir, A.; Jonasdottir, A.; Wong, W. S.; Sigurdsson, G.; Walters, G. B.; Steinberg, S.; Helgason, H.; Thorleifsson, G.; Gudbjartsson, D. F.; Helgason, A.; Magnusson, O. T.;
216:
from one generation to the next. Damage can occur from chemical addition (adduct), or structural disruption to a base of DNA (creating an abnormal nucleotide or nucleotide fragment), or a break in one or both DNA strands. Such DNA damage may result in mutation. When DNA containing damage is
326:
episodes occurring in a mammalian cell per day is high (more than 60,000 per day). Frequent occurrence of DNA damage is likely a problem for all DNA- containing organisms, and the need to cope with DNA damage and minimize their deleterious effects is likely a fundamental problem for life.
334:
past a DNA damage site in the template strand during DNA replication. This process can overcome potentially lethal blockages, but at the cost of introducing inaccuracies in daughter DNA. The causal relationship of DNA damage to spontaneous mutation is illustrated by aerobically growing
371:
sites in DNA are estimated to be depurinated each day in a cell. Numerous DNA repair pathways exist for DNA; however, if the apurinic site is not repaired, misincorporation of nucleotides may occur during replication. Adenine is preferentially incorporated by DNA polymerases in an
339:
bacteria, in which 89% of spontaneously occurring base substitution mutations are caused by reactive oxygen species (ROS)-induced DNA damage. In yeast, more than 60% of spontaneous single-base pair substitutions and deletions are likely caused by trans-lesion synthesis.
306:, an emergency repair process that is also error-prone, thereby generating mutations. In mammalian cells, stalling of replication at damaged sites induces a number of rescue mechanisms that help bypass DNA lesions, however, this may also result in errors. The Y family of
270:, or the causative agent, involved. Most mutagens act either directly, or indirectly via mutagenic metabolites, on an organism's DNA, producing lesions. Some mutagens, however, may affect the replication or chromosomal partition mechanism, and other cellular processes.
88:. It can also be achieved experimentally using laboratory procedures. A mutagen is a mutation-causing agent, be it chemical or physical, which results in an increased rate of mutations in an organism's genetic code. In nature mutagenesis can lead to cancer and various
314:(TLS) whereby these lesion-bypass polymerases replace the stalled high-fidelity replicative DNA polymerase, transit the lesion and extend the DNA until the lesion has been passed so that normal replication can resume; these processes may be error-prone or error-free.
249:
In humans, an average of 60 new mutations are transmitted from parent to offspring. Human males, however, tend to pass on more mutations depending on their age, transmitting an average of two new mutations to their progeny with every additional year of their age.
297:
may substitute for thymine in replication. Metals such as cadmium, chromium, and nickel can increase mutagenesis in a number of ways in addition to direct DNA damage, for example reducing the ability to repair errors, as well as producing epigenetic changes.
350:
In general, it appears that the main underlying cause of spontaneous mutation is error-prone trans-lesion synthesis during DNA replication and that the error-prone non-homologous end-joining repair pathway may also be an important contributor in eukaryotes.
2425:
Mohanasundaram, Boominathan; Rajmane, Vyankatesh B.; Jogdand, Sukanya V.; Bhide, Amey J.; Banerjee, Anjan K. (June 2019). "Agrobacterium-mediated Tnt1 mutagenesis of moss protonemal filaments and generation of stable mutants with impaired gametophyte".
144:. Muller observed a number of chromosome rearrangements in his experiments, and suggested mutation as a cause of cancer. The association of exposure to radiation and cancer had been observed as early as 1902, six years after the discovery of X-ray by
301:
Mutations often arise as a result of problems caused by DNA lesions during replication, resulting in errors in replication. In bacteria, extensive damage to DNA due to mutagens results in single-stranded DNA gaps during replication. This induces the
292:
While most mutagens produce effects that ultimately result in errors in replication, for example creating adducts that interfere with replication, some mutagens may directly affect the replication process or reduce its fidelity. Base analog such as
555:
after activation by UV radiation, and nitrous acid. Interstrand cross-linking (between two strands) causes more damage, as it blocks replication and transcription and can cause chromosomal breakages and rearrangements. Some crosslinkers such as
180:(PAH). PAHs by themselves are not carcinogenic, and it was proposed in 1950 that the carcinogenic forms of PAHs are the oxides produced as metabolites from cellular processes. The metabolic process was identified in 1960s as catalysis by
266:, or through error in DNA replication and repair. Mutagenesis may also occur as a result of the presence of environmental mutagens that induce changes to an organism's DNA. The mechanism by which mutation occurs varies according to the
506:
726:
Research in eukaryotic cells is much scarcer, but chromosomal events seem also to be rather relevant: while an ectopic intrachromosomal recombination has been reported to be involved in acquisition of resistance to 5-fluorocytosine in
616:
Clinically, whether a tumor has formed as a direct consequence of UV radiation is discernible via DNA sequencing analysis for the characteristic context-specific dimerization pattern that occurs due to excessive exposure to sunlight.
246:
mutant strains with useful properties. Initially, the ability of radiation and chemical mutagens to cause mutation was exploited to generate random mutations, but later techniques were developed to introduce specific mutations.
551:; crosslinking of DNA may affect both the replication and the transcription of DNA, and it may be caused by exposure to a variety of agents. Some naturally occurring chemicals may also promote crosslinking, such as
476:
may require the catalytic reaction of cytochrome-P450 for the formation of a reactive alkyl cation. N and O of guanine and the N and N of adenine are most susceptible to attack. N-guanine adducts form the bulk of
409:) forms of adenine and cytosine can result in the rarer imino (=NH) forms. In DNA replication, tautomerization alters the base-pairing sites and can cause the improper pairing of nucleic acid bases.
1458:"The Landscape of Phenotypic and Transcriptional Responses to Ciprofloxacin in Acinetobacter baumannii : Acquired Resistance Alleles Modulate Drug-Induced SOS Response and Prophage Replication"
188:, or product molecules resulting from the reaction of DNA and, in this case, cytochrome P450; the mechanism by which the PAH adducts give rise to mutation, however, is still under investigation.
1456:
Geisinger, Edward; Vargas-Cuebas, Germán; Mortman, Nadav J.; Syal, Sapna; Dai, Yunfei; Wainwright, Elizabeth L.; Lazinski, David; Wood, Stephen; Zhu, Zeyu (2019-06-11). Miller, Samuel I. (ed.).
2469:
Aghapour, Zahra; Gholizadeh, Pourya; Ganbarov, Khudaverdi; bialvaei, Abed Zahedi; Mahmood, Suhad Saad; Tanomand, Asghar; Yousefi, Mehdi; Asgharzadeh, Mohammad; Yousefi, Bahman (April 2019).
1818:
Aghapour, Zahra; Gholizadeh, Pourya; Ganbarov, Khudaverdi; bialvaei, Abed Zahedi; Mahmood, Suhad Saad; Tanomand, Asghar; Yousefi, Mehdi; Asgharzadeh, Mohammad; Yousefi, Bahman (April 2019).
597:, which promotes the formation of a cyclobutyl ring between adjacent thymines in DNA. In human skin cells, thousands of dimers may be formed in a day due to normal exposure to sunlight.
489:, while O-methylthymine can be mispaired with guanine. The type of the mutation generated, however, may be dependent on the size and type of the adduct as well as the DNA sequence.
1055:
2233:
Loechler, E. L. (1996). "The role of adduct site-specific mutagenesis in understanding how carcinogen-DNA adducts cause mutations: Perspective, prospects and problems".
1751:
Quinto-Alemany, David; Canerina-Amaro, Ana; Hernández-Abad, Luís G.; Machín, Félix; Romesberg, Floyd E.; Gil-Lamaignere, Cristina (2012-07-31). Sturtevant, Joy (ed.).
1516:
Quinto-Alemany, David; Canerina-Amaro, Ana; Hernández-Abad, Luís G.; Machín, Félix; Romesberg, Floyd E.; Gil-Lamaignere, Cristina (2012-07-31). Sturtevant, Joy (ed.).
927:
124:
found that "high temperatures" have the ability to mutate genes in the early 1920s, and in 1927, demonstrated a causal link to mutation upon experimenting with an
2127:"Formation of stable adducts and absence of depurinating DNA adducts in cells and DNA treated with the potent carcinogen dibenzoa, lpyrene or its diol epoxides"
521:
may produce highly reactive free radicals that can break the bonds in the DNA. Double-stranded breakages are especially damaging and hard to repair, producing
277:
Many chemical mutagens require biological activation to become mutagenic. An important group of enzymes involved in the generation of mutagenic metabolites is
643:
in DNA during replication more likely to occur since the bonding between the strands is made less stable by the stretching. Forward slippage will result in
176:
to be a cause of cancer as early as 1775, and coal tar was demonstrated to cause cancer in 1915. The chemicals involved in both were later shown to be
744:
20:
1424:"Induction of microsomal enzymes by foreign chemicals and carcinogenesis by polycyclic aromatic hydrocarbons: G. H. A. Clowes Memorial Lecture"
2376:
Mata, Douglas A.; Williams, Erik A.; Sokol, Ethan; Oxnard, Geoffrey R.; Fleischmann, Zoe; Tse, Julie Y.; Decker, Brennan (23 March 2022).
688:
or retrotransposons may insert DNA sequences into coding regions or functional elements of a gene and result in inactivation of the gene.
2109:
1878:
405:
forms. For example, the keto (C=O) forms of guanine and thymine can rearrange into their rare enol (-OH) forms, while the amino (-NH
601:
may help bypass these lesions in an error-free manner; however, individuals with defective DNA repair function, such as those with
808:
753:
Early methods of mutagenesis produced entirely random mutations; however, modern methods of mutagenesis are capable of producing
323:
238:
383:
to uridine at one five-hundredth of the rate of depurination and can result in G to A transition. Eukaryotic cells also contain
1094:
790:
177:
462:
of the DNA; it is, however, uncertain how significant such depurination as caused by the adducts is in generating mutation.
116:
DNA may be modified, either naturally or artificially, by a number of physical, chemical and biological agents, resulting in
1584:
723:
spp. Chromosomal events, specially gene amplification, seem also to be relevant to this adaptive mutagenesis in bacteria.
547:
Covalent bonds between the bases of nucleotides in DNA, be they in the same strand or opposing strands, is referred to as
533:
that can damage DNA. Incorrect repair of other damage induced by the highly reactive species can also lead to mutations.
485:
of O-adduct of guanine may be poor in some tissues such as the brain. The O methylation of guanine can result in G to A
780:
707:
resistance to ciprofloxacin. Resistance mechanisms are presumed to be linked to chromosomal mutation untransferable via
626:
525:
and deletion of part of a chromosome. Alkylating agents like mustard gas may also cause breakages in the DNA backbone.
258:
Mutagenesis may occur endogenously (e.g. spontaneous hydrolysis), through normal cellular processes that can generate
913:
344:
222:
237:
Mammalian nuclear DNA may sustain more than 60,000 damage episodes per cell per day, as listed with references in
942:"Genetics and Genomics Timeline 1927 Hermann J. Muller (1890-1967) demonstrates that X rays can induce mutations"
766:
754:
522:
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bacteria, while modulation of the SOS response and endogenous prophage DNA synthesis has been shown to increase
1896:"Genetic and epigenetic mechanisms in metal carcinogenesis and cocarcinogenesis: nickel, arsenic, and chromium"
708:
242:
217:
replicated, an incorrect base may be inserted in the new complementary strand as it is being synthesized (see
956:
775:
676:
530:
454:
259:
133:
425:, thus altering the expression of the marked gene without incurring a mutation to the DNA sequence itself.
785:
450:
289:. Mutagens that are not mutagenic by themselves but require biological activation are called promutagens.
2522:"Adaptive mutation and amplification in Escherichia coli: two pathways of genome adaptation under stress"
387:, thought to be involved in the control of gene transcription, which can become deaminated into thymine.
1329:"Nature and Nurture — Lessons from Chemical Carcinogenesis: Chemical Carcinogens — From Past to Present"
602:
486:
209:
121:
97:
1308:
Yamagawa K, Ichikawa K (1915). "Experimentelle Studie ueber die
Pathogenese der Epithel geschwuelste".
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allows them to insert between bases in DNA. This insert causes the DNA's backbone to stretch and makes
19:
This article is about mutagenesis as a general process. For mutagenesis as a laboratory technique, see
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Tautomerization is the process by which compounds spontaneously rearrange themselves to assume their
1997:
1665:"Endogenous carcinogenesis: Molecular oncology into the twenty-first century--presidential address"
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542:
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1978:
1733:
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An additional significant source of mutations in eukaryotes is the inaccurate DNA repair process
161:
156:, Muller's contemporary, also showed the effect of X-rays on mutations in barley in 1928, and of
101:
1664:
145:
1121:"Historical Development of the Linear Nonthreshold Dose-Response Model as Applied to Radiation"
481:, but they appear to be non-mutagenic. Alkylation at O of guanine, however, is harmful because
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Melendez-Colon, V. J.; Smith, C. A.; Seidel, A.; Luch, A.; Platt, K. L.; Baird, W. M. (1997).
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32:
2630:"What is mutation? A chapter in the series: How microbes "jeopardize" the modern synthesis"
1753:"Yeasts Acquire Resistance Secondary to Antifungal Drug Treatment by Adaptive Mutagenesis"
1518:"Yeasts Acquire Resistance Secondary to Antifungal Drug Treatment by Adaptive Mutagenesis"
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364:
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149:
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Longerich, S.; Galloway, A. M.; Harris, R. S.; Wong, C.; Rosenberg, S. M. (1995-12-19).
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consists of the bonding of two monomers to form an oligomer, such as the formation of
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1965:
1944:
1142:
1056:"Muller's Nobel lecture on dose–response for ionizing radiation:ideology or science?"
838:
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431:
373:
294:
153:
125:
2455:
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1737:
1700:
Heidenreich, Erich (January 2007). "Adaptive
Mutation in Saccharomyces cerevisiae".
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1982:
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Hersh, Megan N; Ponder, Rebecca G; Hastings, P.J; Rosenberg, Susan M (June 2004).
2017:
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Mitteilungen aus der
Medizinischen Fakultät der Kaiserlichen Universität zu Tokyo
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Ionizing radiation and reactive oxygen species often oxidize guanine to produce
478:
473:
380:
169:
157:
2439:
2268:
Setlow, R. B. (1966). "Cyclobutane-type pyrimidine dimers in polynucleotides".
2131:
Proceedings of the
National Academy of Sciences of the United States of America
1382:
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1120:
983:
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1713:
1605:"Rate of de novo mutations and the importance of father's age to disease risk"
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813:
681:
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465:
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Bases may be modified endogenously by normal cellular molecules. For example,
331:
311:
263:
231:
226:
218:
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2587:
2151:
1786:
1721:
1551:
1481:
1367:
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1216:; Robson, J.M.; Carr, J.G. (March 1947). "Chemical Production of Mutations".
1147:"Genetic Effects of Ultra-Violet Radiation in Maize. I. Unfiltered Radiation"
818:
667:, blocking replication as well as causing mitotic homologous recombination.
565:
552:
469:
446:
225:, which produces mutations. Mutations can ordinarily be avoided if accurate
137:
93:
2673:
2547:
2506:
2471:"Molecular mechanisms related to colistin resistance in Enterobacteriaceae"
2447:
2411:
2362:
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1974:
1929:
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1820:"Molecular mechanisms related to colistin resistance in Enterobacteriaceae"
1804:
1729:
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1408:
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of bases can cause errors in replication. Some alkylating agents such as N-
2614:
2297:
2254:
2170:
2035:
1683:
1473:
1439:
1040:
898:
865:"The Discovery of Mustard Gas Mutagenesis by Auerbach and Robson in 1941"
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757:. Modern laboratory techniques used to generate these mutations include:
396:
213:
205:
184:, which produces reactive species that can interact with the DNA to form
117:
81:
77:
2487:
1836:
1628:
1276:
1261:"Percivall Pott (1714-1788) and Chimney Sweepers' Cancer of the Scrotum"
505:
2378:"Prevalence of UV Mutational Signatures Among Cutaneous Primary Tumors"
823:
426:
267:
85:
84:. It may occur spontaneously in nature, or as a result of exposure to
2563:"Adaptive mutation sequences reproduced by mismatch repair deficiency"
2066:
1911:
2344:
2184:
Boysen, G.; Pachkowski, B. F.; Nakamura, J.; Swenberg, J. A. (2009).
368:
281:. Other enzymes that may also produce mutagenic metabolites include
185:
1344:"The biological significance of metabolism of polycyclic compounds"
914:"Hermann Joseph Muller's Study of X-rays as a Mutagen, (1926-1927)"
2190:
Mutation
Research/Genetic Toxicology and Environmental Mutagenesis
685:
607:
504:
141:
2186:"The Formation and Biological Significance of N7-Guanine Adducts"
1945:"Impact of reactive oxygen species on spontaneous mutagenesis in
572:
because of their high degree of toxicity to proliferating cells.
731:, genome duplications have been found to confer resistance in
96:. Mutagenesis as a science was developed based on work done by
197:
612:
Ethidium intercalated between two adenine-thymine base pairs.
605:, are sensitive to sunlight and may be prone to skin cancer.
2051:"DNA resection in eukaryotes: deciding how to fix the break"
347:, that is often employed in repair of double strand breaks.
38:
1585:"Older fathers pass on more genetic mutations, study shows"
53:
44:
50:
363:
of the DNA can occur. Under physiological conditions the
196:
DNA damage is an abnormal alteration in the structure of
65:
59:
2628:
Rosenberg, Susan M.; Fitzgerald, Devon M. (2019-04-01).
509:
Arrows indicates chromosomal breakages due to DNA damage
1943:
Sakai A, Nakanishi M, Yoshiyama K, Maki H (July 2006).
1702:
Critical
Reviews in Biochemistry and Molecular Biology
711:
76:) is a process by which the genetic information of an
1998:"DNA sequence analysis of spontaneous mutagenesis in
310:
specializes in DNA lesion bypass in a process termed
68:
62:
56:
359:
DNA is not entirely stable in aqueous solution, and
41:
47:
35:
1007:"Seventy Years Ago: Mutation Becomes Experimental"
1996:Kunz BA, Ramachandran K, Vonarx EJ (April 1998).
1871:Chemical Carcinogenesis (Current Cancer Research)
212:that can be replicated; hence, a mutation can be
2567:Proceedings of the National Academy of Sciences
663:interferes with the functioning of the enzyme
2321:"DNA repair: How to accurately bypass damage"
1603:Thorsteinsdottir, U.; Stefansson, K. (2012).
330:Most spontaneous mutations likely arise from
192:Distinction between a mutation and DNA damage
8:
1451:
1449:
926:: CS1 maint: numeric names: authors list (
647:, while reverse slippage will result in an
367:may be hydrolyzed spontaneously and 10,000
160:(UV) radiation on maize in 1936. In 1940s,
631:The planar structure of chemicals such as
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745:Mutagenesis (molecular biology technique)
172:can also cause mutations in fruit flies.
21:Mutagenesis (molecular biology technique)
912:Kevin M. Gleason Published: 2017-03-07.
200:that cannot, itself, be replicated when
148:, and the discovery of radioactivity by
1894:Salnikow K, Zhitkovich (January 2008).
1658:
1656:
855:
108:in the first half of the 20th century.
1383:"A new cytochrome in liver microsomes"
1265:British Journal of Industrial Medicine
1259:Brown, J. R.; Thornton, J. L. (1957).
1125:University of New Hampshire Law Review
957:"Artificial Transmutation of the Gene"
919:
651:. Also, the intercalation into DNA of
1695:
1693:
1511:
1509:
7:
1005:Crow, J. F.; Abrahamson, S. (1997).
92:, and it is also a driving force of
1387:The Journal of Biological Chemistry
1119:Ronald L. Kathren (December 2002).
318:DNA damage and spontaneous mutation
2104:. Academic Press. pp. 17–20.
332:error-prone trans-lesion synthesis
274:lacking in an essential nutrient
219:DNA repair § Translesion synthesis
80:is changed by the production of a
14:
2394:10.1001/jamanetworkopen.2022.3833
2319:Broyde, S.; Patel, D. J. (2010).
1054:Calabrese, E. J. (30 June 2011).
1966:10.1111/j.1365-2443.2006.00982.x
809:DNA damage (naturally occurring)
239:DNA damage (naturally occurring)
178:polycyclic aromatic hydrocarbons
31:
2428:Molecular Genetics and Genomics
1900:Chemical Research in Toxicology
791:Sequence saturation mutagenesis
735:to nutrient-poor environments.
692:Adaptive mutagenesis mechanisms
2202:10.1016/j.mrgentox.2009.05.006
1145:; G. F. Sprague (1936-10-15).
441:Many compounds, such as PAHs,
1:
2475:Infection and Drug Resistance
1824:Infection and Drug Resistance
1400:10.1016/S0021-9258(18)60338-2
1348:Biochemical Society Symposium
2647:10.1371/journal.pgen.1007995
2539:10.1016/j.resmic.2004.01.020
2290:10.1126/science.153.3734.379
1778:10.1371/journal.pone.0042279
1583:Jha, Alok (22 August 2012).
1543:10.1371/journal.pone.0042279
1381:Omura, T.; Sato, R. (1962).
1238:10.1126/science.105.2723.243
1154:Proc. Natl. Acad. Sci. U.S.A
781:Signature tagged mutagenesis
627:Intercalation (biochemistry)
2098:Sinden, Richard R. (1994).
2018:10.1093/genetics/148.4.1491
1023:10.1093/genetics/147.4.1491
621:Intercalation between bases
593:as a result of exposure to
2709:
2440:10.1007/s00438-019-01532-4
2101:DNA Structure and Function
2049:Huertas P (January 2010).
1869:Trevor M. Penning (2011).
984:10.1126/science.66.1699.84
881:10.1093/genetics/134.2.393
742:
695:
674:
624:
579:
540:
498:
394:
345:non-homologous end joining
223:non-homologous end joining
18:
1714:10.1080/10409230701507773
1075:10.1007/s00204-011-0728-8
767:Site-directed mutagenesis
529:may also generate highly
379:Cytidine may also become
283:glutathione S-transferase
243:resistance to antibiotics
132:changes when irradiating
2588:10.1073/pnas.92.26.12017
2526:Research in Microbiology
2152:10.1073/pnas.94.25.13542
2000:Saccharomyces cerevisiae
729:Saccharomyces cerevisiae
709:horizontal gene transfer
2247:10.1093/carcin/17.5.895
776:Insertional mutagenesis
755:site-specific mutations
739:Laboratory applications
705:Acinetobacter baumannii
677:Insertional mutagenesis
671:Insertional mutagenesis
568:are used as anticancer
531:reactive oxygen species
455:reactive oxygen species
451:pyrrolizidine alkaloids
260:reactive oxygen species
2055:Nat. Struct. Mol. Biol
1422:Conney, A. H. (1982).
1327:Luch, Andreas (2005).
1175:10.1073/pnas.22.10.572
1063:Archives of Toxicology
955:Muller, H. J. (1927).
786:Transposon mutagenesis
613:
510:
355:Spontaneous hydrolysis
232:the article DNA repair
1474:10.1128/mBio.01127-19
611:
603:xeroderma pigmentosum
508:
419:DNA may be methylated
413:Modification of bases
312:translesion synthesis
210:nucleic acid sequence
1663:Loeb, L. A. (1989).
762:Directed mutagenesis
427:Histone modification
423:S-adenosylmethionine
2579:1995PNAS...9212017L
2573:(26): 12017–12020.
2488:10.2147/idr.s199844
2337:2010Natur.465.1023B
2331:(7301): 1023–1024.
2282:1966Sci...153..379S
2143:1997PNAS...9413542M
2137:(25): 13542–13547.
1837:10.2147/idr.s199844
1769:2012PLoSO...742279Q
1629:10.1038/nature11396
1621:2012Natur.488..471K
1534:2012PLoSO...742279Q
1277:10.1136/oem.14.1.68
1230:1947Sci...105..243A
1166:1936PNAS...22..572S
976:1927Sci....66...84M
713:E. coli, Salmonella
549:crosslinking of DNA
543:Crosslinking of DNA
208:is a change in the
1342:Boyland E (1950).
863:Beale, G. (1993).
649:insertion mutation
614:
519:Ionizing radiation
511:
162:Charlotte Auerbach
102:Charlotte Auerbach
90:heritable diseases
16:Biological process
2382:JAMA Network Open
2067:10.1038/nsmb.1710
1912:10.1021/tx700198a
1678:(20): 5489–5496.
1615:(7412): 471–475.
1434:(12): 4875–4917.
834:Mutation breeding
698:Adaptive mutation
645:deletion mutation
591:pyrimidine dimers
403:structural isomer
287:epoxide hydrolase
204:. In contrast, a
136:with relatively
2700:
2678:
2677:
2667:
2649:
2625:
2619:
2618:
2608:
2590:
2558:
2552:
2551:
2541:
2517:
2511:
2510:
2500:
2490:
2466:
2460:
2459:
2422:
2416:
2415:
2405:
2373:
2367:
2366:
2356:
2345:10.1038/4651023a
2316:
2310:
2309:
2276:(734): 379–386.
2265:
2259:
2258:
2230:
2224:
2223:
2213:
2181:
2175:
2174:
2164:
2154:
2122:
2116:
2115:
2095:
2089:
2088:
2078:
2046:
2040:
2039:
2029:
1993:
1987:
1986:
1968:
1947:Escherichia coli
1940:
1934:
1933:
1923:
1891:
1885:
1884:
1866:
1860:
1859:
1849:
1839:
1815:
1809:
1808:
1798:
1780:
1748:
1742:
1741:
1697:
1688:
1687:
1669:
1660:
1651:
1650:
1640:
1599:
1593:
1592:
1580:
1574:
1573:
1563:
1545:
1513:
1504:
1503:
1493:
1453:
1444:
1443:
1419:
1413:
1412:
1402:
1393:(4): 1375–1376.
1378:
1372:
1371:
1339:
1333:
1332:
1324:
1318:
1317:
1305:
1299:
1298:
1288:
1256:
1250:
1249:
1210:
1204:
1203:
1201:
1200:
1187:
1177:
1151:
1139:
1133:
1132:
1116:
1110:
1109:
1107:
1105:
1100:on 2 August 2017
1099:
1093:. Archived from
1069:(4): 1495–1498.
1060:
1051:
1045:
1044:
1034:
1017:(4): 1491–1496.
1002:
996:
995:
961:
952:
946:
945:
938:
932:
931:
925:
917:
909:
903:
902:
892:
860:
665:topoisomerase II
633:ethidium bromide
599:DNA polymerase η
570:chemotherapeutic
558:cyclophosphamide
527:Oxidative stress
385:5-methylcytosine
75:
74:
71:
70:
67:
64:
61:
58:
55:
52:
49:
46:
43:
40:
37:
2708:
2707:
2703:
2702:
2701:
2699:
2698:
2697:
2683:
2682:
2681:
2640:(4): e1007995.
2627:
2626:
2622:
2560:
2559:
2555:
2519:
2518:
2514:
2468:
2467:
2463:
2424:
2423:
2419:
2375:
2374:
2370:
2318:
2317:
2313:
2267:
2266:
2262:
2232:
2231:
2227:
2183:
2182:
2178:
2124:
2123:
2119:
2112:
2097:
2096:
2092:
2048:
2047:
2043:
2012:(4): 1491–505.
1995:
1994:
1990:
1942:
1941:
1937:
1893:
1892:
1888:
1881:
1868:
1867:
1863:
1817:
1816:
1812:
1750:
1749:
1745:
1699:
1698:
1691:
1672:Cancer Research
1667:
1662:
1661:
1654:
1601:
1600:
1596:
1582:
1581:
1577:
1515:
1514:
1507:
1455:
1454:
1447:
1428:Cancer Research
1421:
1420:
1416:
1380:
1379:
1375:
1341:
1340:
1336:
1326:
1325:
1321:
1307:
1306:
1302:
1258:
1257:
1253:
1224:(2723): 243–7.
1212:
1211:
1207:
1198:
1196:
1149:
1141:
1140:
1136:
1118:
1117:
1113:
1103:
1101:
1097:
1058:
1053:
1052:
1048:
1004:
1003:
999:
970:(1699): 84–87.
959:
954:
953:
949:
940:
939:
935:
918:
911:
910:
906:
862:
861:
857:
853:
848:
799:
771:PCR mutagenesis
747:
741:
700:
694:
679:
673:
629:
623:
584:
578:
545:
539:
516:
514:Backbone damage
503:
483:excision repair
443:aromatic amines
436:reducing sugars
415:
408:
399:
393:
365:glycosidic bond
357:
320:
308:DNA polymerases
285:and microsomal
279:cytochrome P450
256:
194:
182:cytochrome P450
150:Henri Becquerel
146:Wilhelm Röntgen
114:
34:
30:
24:
17:
12:
11:
5:
2706:
2704:
2696:
2695:
2685:
2684:
2680:
2679:
2620:
2553:
2532:(5): 352–359.
2512:
2461:
2434:(3): 583–596.
2417:
2388:(3): e223833.
2368:
2311:
2260:
2241:(5): 895–902.
2235:Carcinogenesis
2225:
2176:
2117:
2111:978-0126457506
2110:
2090:
2041:
1988:
1935:
1886:
1880:978-1617379949
1879:
1861:
1810:
1743:
1708:(4): 285–311.
1689:
1652:
1594:
1575:
1505:
1445:
1414:
1373:
1334:
1319:
1300:
1251:
1205:
1143:Stadler, L. J.
1134:
1111:
1046:
997:
947:
933:
904:
875:(2): 393–399.
854:
852:
849:
847:
846:
841:
836:
831:
826:
821:
816:
811:
806:
804:Carcinogenesis
800:
798:
795:
794:
793:
788:
783:
778:
773:
764:
743:Main article:
740:
737:
696:Main article:
693:
690:
675:Main article:
672:
669:
653:anthracyclines
625:Main article:
622:
619:
580:Main article:
577:
574:
541:Main article:
538:
535:
515:
512:
458:result in the
414:
411:
406:
395:Main article:
392:
389:
356:
353:
322:The number of
319:
316:
255:
252:
202:DNA replicates
193:
190:
122:Hermann Muller
113:
110:
98:Hermann Muller
15:
13:
10:
9:
6:
4:
3:
2:
2705:
2694:
2691:
2690:
2688:
2675:
2671:
2666:
2661:
2657:
2653:
2648:
2643:
2639:
2635:
2634:PLOS Genetics
2631:
2624:
2621:
2616:
2612:
2607:
2602:
2598:
2594:
2589:
2584:
2580:
2576:
2572:
2568:
2564:
2557:
2554:
2549:
2545:
2540:
2535:
2531:
2527:
2523:
2516:
2513:
2508:
2504:
2499:
2494:
2489:
2484:
2480:
2476:
2472:
2465:
2462:
2457:
2453:
2449:
2445:
2441:
2437:
2433:
2429:
2421:
2418:
2413:
2409:
2404:
2399:
2395:
2391:
2387:
2383:
2379:
2372:
2369:
2364:
2360:
2355:
2350:
2346:
2342:
2338:
2334:
2330:
2326:
2322:
2315:
2312:
2307:
2303:
2299:
2295:
2291:
2287:
2283:
2279:
2275:
2271:
2264:
2261:
2256:
2252:
2248:
2244:
2240:
2236:
2229:
2226:
2221:
2217:
2212:
2207:
2203:
2199:
2195:
2191:
2187:
2180:
2177:
2172:
2168:
2163:
2158:
2153:
2148:
2144:
2140:
2136:
2132:
2128:
2121:
2118:
2113:
2107:
2103:
2102:
2094:
2091:
2086:
2082:
2077:
2072:
2068:
2064:
2060:
2056:
2052:
2045:
2042:
2037:
2033:
2028:
2023:
2019:
2015:
2011:
2007:
2003:
2001:
1992:
1989:
1984:
1980:
1976:
1972:
1967:
1962:
1959:(7): 767–78.
1958:
1954:
1950:
1948:
1939:
1936:
1931:
1927:
1922:
1917:
1913:
1909:
1905:
1901:
1897:
1890:
1887:
1882:
1876:
1872:
1865:
1862:
1857:
1853:
1848:
1843:
1838:
1833:
1829:
1825:
1821:
1814:
1811:
1806:
1802:
1797:
1792:
1788:
1784:
1779:
1774:
1770:
1766:
1763:(7): e42279.
1762:
1758:
1754:
1747:
1744:
1739:
1735:
1731:
1727:
1723:
1719:
1715:
1711:
1707:
1703:
1696:
1694:
1690:
1685:
1681:
1677:
1673:
1666:
1659:
1657:
1653:
1648:
1644:
1639:
1634:
1630:
1626:
1622:
1618:
1614:
1610:
1606:
1598:
1595:
1590:
1586:
1579:
1576:
1571:
1567:
1562:
1557:
1553:
1549:
1544:
1539:
1535:
1531:
1528:(7): e42279.
1527:
1523:
1519:
1512:
1510:
1506:
1501:
1497:
1492:
1487:
1483:
1479:
1475:
1471:
1467:
1463:
1459:
1452:
1450:
1446:
1441:
1437:
1433:
1429:
1425:
1418:
1415:
1410:
1406:
1401:
1396:
1392:
1388:
1384:
1377:
1374:
1369:
1365:
1361:
1357:
1353:
1349:
1345:
1338:
1335:
1330:
1323:
1320:
1315:
1311:
1304:
1301:
1296:
1292:
1287:
1282:
1278:
1274:
1270:
1266:
1262:
1255:
1252:
1247:
1243:
1239:
1235:
1231:
1227:
1223:
1219:
1215:
1209:
1206:
1195:
1191:
1186:
1181:
1176:
1171:
1167:
1163:
1160:(10): 572–8.
1159:
1155:
1148:
1144:
1138:
1135:
1130:
1126:
1122:
1115:
1112:
1096:
1092:
1088:
1084:
1080:
1076:
1072:
1068:
1064:
1057:
1050:
1047:
1042:
1038:
1033:
1028:
1024:
1020:
1016:
1012:
1008:
1001:
998:
993:
989:
985:
981:
977:
973:
969:
965:
958:
951:
948:
943:
937:
934:
929:
923:
915:
908:
905:
900:
896:
891:
886:
882:
878:
874:
870:
866:
859:
856:
850:
845:
842:
840:
839:Mutation rate
837:
835:
832:
830:
827:
825:
822:
820:
817:
815:
812:
810:
807:
805:
802:
801:
796:
792:
789:
787:
784:
782:
779:
777:
774:
772:
768:
765:
763:
760:
759:
758:
756:
751:
746:
738:
736:
734:
733:S. cerevisiae
730:
724:
722:
718:
714:
710:
706:
699:
691:
689:
687:
683:
678:
670:
668:
666:
662:
658:
654:
650:
646:
642:
638:
634:
628:
620:
618:
610:
606:
604:
600:
596:
592:
588:
583:
575:
573:
571:
567:
563:
559:
554:
550:
544:
536:
534:
532:
528:
524:
523:translocation
520:
513:
507:
502:
497:
495:
490:
488:
484:
480:
475:
471:
467:
463:
461:
456:
452:
448:
444:
439:
437:
433:
428:
424:
420:
412:
410:
404:
398:
390:
388:
386:
382:
377:
375:
374:apurinic site
370:
366:
362:
354:
352:
348:
346:
341:
338:
333:
328:
325:
317:
315:
313:
309:
305:
299:
296:
295:5-bromouracil
290:
288:
284:
280:
275:
271:
269:
265:
261:
253:
251:
247:
244:
240:
235:
233:
228:
224:
220:
215:
211:
207:
203:
199:
191:
189:
187:
183:
179:
173:
171:
167:
163:
159:
155:
154:Lewis Stadler
151:
147:
143:
139:
135:
131:
127:
126:x-ray machine
123:
119:
111:
109:
107:
103:
99:
95:
91:
87:
83:
79:
73:
28:
22:
2637:
2633:
2623:
2570:
2566:
2556:
2529:
2525:
2515:
2478:
2474:
2464:
2431:
2427:
2420:
2385:
2381:
2371:
2328:
2324:
2314:
2273:
2269:
2263:
2238:
2234:
2228:
2196:(2): 76–94.
2193:
2189:
2179:
2134:
2130:
2120:
2100:
2093:
2058:
2054:
2044:
2009:
2005:
1999:
1991:
1956:
1952:
1946:
1938:
1906:(1): 28–44.
1903:
1899:
1889:
1873:. Springer.
1870:
1864:
1827:
1823:
1813:
1760:
1756:
1746:
1705:
1701:
1675:
1671:
1612:
1608:
1597:
1589:The Guardian
1588:
1578:
1525:
1521:
1465:
1461:
1431:
1427:
1417:
1390:
1386:
1376:
1351:
1347:
1337:
1322:
1313:
1309:
1303:
1271:(1): 68–70.
1268:
1264:
1254:
1221:
1217:
1214:Auerbach, C.
1208:
1197:. Retrieved
1157:
1153:
1137:
1128:
1124:
1114:
1102:. Retrieved
1095:the original
1066:
1062:
1049:
1014:
1010:
1000:
967:
963:
950:
936:
907:
872:
868:
858:
844:Transfection
752:
748:
732:
728:
725:
721:Enterobacter
720:
716:
712:
704:
701:
680:
657:daunorubicin
630:
615:
595:UV radiation
587:Dimerization
585:
576:Dimerization
546:
537:Crosslinking
517:
494:8-oxoguanine
491:
474:Nitrosamines
464:
460:depurination
440:
432:glycosylated
416:
400:
378:
361:depurination
358:
349:
342:
336:
329:
321:
304:SOS response
300:
291:
276:
272:
257:
248:
236:
195:
174:
166:J. M. Robson
130:phylogenetic
115:
106:J. M. Robson
26:
25:
2693:Mutagenesis
2481:: 965–975.
2061:(1): 11–6.
1953:Genes Cells
1830:: 965–975.
1331:. Medscape.
1104:30 December
682:Transposons
661:doxorubicin
562:mitomycin C
501:Epigenetics
479:DNA adducts
453:, may form
391:Tautomerism
264:DNA adducts
170:mustard gas
168:found that
158:ultraviolet
134:fruit flies
27:Mutagenesis
1316:: 295–344.
1199:2007-10-11
851:References
814:DNA repair
719:spp., and
717:Klebsiella
637:proflavine
499:See also:
487:transition
466:Alkylation
381:deaminated
324:DNA damage
254:Mechanisms
227:DNA repair
2656:1553-7404
2597:0027-8424
1787:1932-6203
1722:1040-9238
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