Mutagenesis, Vol. 14, No. 3, 295-300,
May 1999
© 1999 UK Environmental Mutagen Society/Oxford University Press
The isfA mutation specifically inhibits the SOS-dependent mutagenic pathway and does not selectively affect any particular base substitution
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 5A Pawinskiego Str., 02-106 Warszawa, Poland
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Abstract |
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We have previously described a new mutation in Escherichia coli, isfA, which causes inhibition of SOS mutagenesis (UV-induced in rec+ and spontaneous in recA730 strains) and several SOS-dependent phenomena. Antimutagenic activity of the isfA mutation in the recA730 strain was shown to be related to inhibition of processing of UmuD to UmuD' by RecA* coprotease. In the present study we have analysed the specificity of the antimutagenic activity of the isfA mutation by employing F' plasmids carrying a set of mutant lacZ genes that can individually detect two types of transitions and four types of transversions. Analysis revealed that isfA inhibits UV-induced G:C
A:T and A:TG:C transitions, but does not affect the same G:CA:T transitions induced by EMS, an SOS-independent mutagen. Analysis of the antimutagenic activity of the isfA mutation in two mutator strains, recA730 and mutL, showed that isfA inhibits SOS-dependent transversions in recA730, but not transitions generated as replication errors in the mutL strain. In the double mutant recA730 mutL, both transitions and transversions were enhanced and isfA inhibits most transversions and only those transitions generated by the recA730 mutation. The results indicate that the antimutagenic activity of the isfA mutation is specific for the SOS, UmuD'C-dependent mutagenic pathway but does not selectively affect any particular base substitution. Moreover, studies on the effect of the isfA mutation on transitions and transversions in different genetic backgrounds enable us to recognize different mutagenic pathways active in recA730 cells. |
Introduction |
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In Escherichia coli the inducible SOS system is known to play a key role in the regulation of the cell's response to DNA damage by controlling DNA repair and mutagenesis (for a review see Friedberg et al., 1995
). The major role in the regulation of the SOS response is played by the RecA coprotease (RecA*), activated when DNA replication is arrested at a lesion (Salles and Defais, 1984; Sanssafar and Roberts, 1990).
The RecA coprotease promotes cleavage of the LexA repressor (Ennis et al., 1985; Little, 1991), leading to derepression of >20 genes involved in DNA repair and mutagenesis and of the cleavage of UmuD to UmuD', the form active in mutagenesis (Burckhardt et al.,1988; Nohmi et al., 1988; Shinagawa et al.,1988).
RecA coprotease activity may also be expressed constitutively in certain recA mutants (Castellazzi et al., 1972; Witkin et al., 1982; Wang and Tessman, 1986). One of the most intensely studied is the recA730 Glu38Lys mutant (Witkin et al., 1982; Lavery and Kowalczykowski, 1992; Ennis et al., 1995), which constitutively mediates cleavage of the LexA repressor leading to derepression of the SOS-controlled genes and exhibits a mutator phenotype resulting from cleavage of UmuD (Sweasy et al., 1990; Woodgate and Ennis, 1991).
We have previously described a new mutation in E.coli, isfA, which causes inhibition of SOS mutagenesis (UV- and MMS-induced) and several other SOS-dependent phenomena (resumption of DNA replication in UV-irradiated cells, cell filamentation, prophage induction and an increase in UV sensitivity) (Bebenek and Pietrzykowska, 1995, 1996). The isfA mutation also significantly reduces UV-induced expression of ß-galactosidase from recA::lacZ and umuC::lacZ fusions in rec+ strains (Bebenek and Pietrzykowska, 1995) and inhibits mutator activity of the recA730 strain (Bebenek and Pietrzykowska, 1996). We have shown that introduction of the isfA mutation into recA730 or recA730 lexA51 mutants suppresses the mutator character of these strains by inhibiting processing of UmuD to UmuD' (Bebenek and Pietrzykowska, 1996).
It is well established that the majority of UV-induced mutations are G:CA:T and A:TG:C transitions (Miller, 1985; Schaaper et al., 1987). In contrast, mutations formed in the recA730 strain are mainly transversions (Fijalkowska et al., 1997; Watanabe-Akanuma et al., 1997). Since we have observed that the isfA mutation inhibited both UV-induced mutagenesis in rec+ and spontaneous mutagenesis in recA730 strains, it was proposed that isfA-mediated inhibition is related to the SOS-dependent mutagenic pathway, rather than a type of base substitution(s).
To learn more about the antimutagenic specificity of the isfA mutation we studied, using the lacZ system (Cupples and Miller, 1989), the effect of the isfA mutation on transitions and transversions induced by different mechanisms, both SOS-dependent (UV-induced and generated in the recA730 mutator) and SOS-independent (EMS-induced and in the mutL strain) (Schendel and Defais, 1980; Todd et al., 1981; Kato et al., 1982; Modrich, 1991; Modrich and Lahue, 1996).
We found that the isfA mutation inhibits formation of SOS-dependent transitions and transversions to a similar extent. It does not inhibit transitions resulting from replication of normal DNA, which can be observed in the mutL strain, or of EMS-modified DNA containing O6-ethylguanine. By using the isfA mutation we were able to recognize different mutagenic pathways operating in recA730 cells.
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Materials and methods |
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Bacterial strains
The strains used are listed in Table I
. Original strains CC101–CC106 are derivatives of P90C[ara, 
(lac proB)XIII], each carrying a different lacZ allele on an F'(lacI–, Z– proB+) plasmid and, therefore, exhibiting the Lac– phenotype. These strains enable detection of each of six possible base substitutions (two transitions and four transversions) simply by measuring the number of Lac+ revertants (Cupples and Miller, 1989). Reversion events in the F' ß-galactosidase gene leading to the Lac+ phenotype are listed in Table I.
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Strains JB1501–JB1506 and JB1601–JB1606, used for UV- and EMS-induced mutagenesis are derivatives of CC101–CC106 and were constructed by P1 transduction of zie::Tn10 or isfA zie::Tn10 from JB1001 and selection for tetracycline resistance and UV sensitivity.
Strains used for spontaneous mutagenesis are derivatives of KA796 and have a chromosomal deletion of the lactose operon. JB730 (tets) was obtained by transducing srl+ from SC30 to NR11531 and selection for growth on sorbitol as a carbon source. Strains JB600, JB601, JB731, JB732, JB950 and JB951 were obtained by transducing zie::Tn10 or isfA zie::Tn10 from JB1001 to KA796, JB730 or NR9559 and selection for tetracycline resistance and UV sensitivity. P1 transduction and selection for kanamycin resistance was used to transfer mutL from NR9559 to JB731 and JB732 to obtain JB733 or JB734, respectively. The final series of strains carrying F'101–F'106 plasmids were obtained by mating their F– progenitors with CC101–CC106 donor strains, followed by Pro+ selection on minimal glucose agar plates containing tetracycline or kanamycin or both.
Media
Bacteria were grown in LB medium (Miller, 1972) or in E minimal medium (Vogel and Bonner, 1956) supplemented with 0.4% glucose; 5 µg/ml thiamine was added where necessary. Minimal lactose agar plates (MM-Lac+) and minimal top agar (MM-top) were prepared as described by Watanabe et al. (1994). Solid media contained 1.5% agar and top media contained 0.6% agar. Antibiotics used were 12.5 µg/ml tetracycline, 50 µg/ml kanamycin and 100 µg/ml rifampicin.
Chemicals
Ethyl methane sulfonate (EMS; Merck) was diluted twice in dimethylsulphoxide (DMSO; Fluka) before addition to the top LB or MM-top agar.
UV mutagenesis
UV-induced mutagenesis was performed according to Cupples and Miller (1989). An overnight culture in E minimal medium was diluted 1:50 in fresh LB medium and bacteria grown to a density of 2x108 cells/ml. They were then centrifuged and resuspended in half the original volume of 0.01 M MgSO4. Bacteria were irradiated on a Petri dish with UV light (254 nm). Directly after irradiation, 0.1 ml of appropriate dilution was spread on LB plates to monitor survival. Aliquots of 0.25 ml of irradiated bacteria were inoculated into 5 ml of fresh LB and grown overnight at 37°C with shaking. Samples of 0.1 ml of overnight cultures were spread on MM-Lac+ plates for Lac+ revertants and on LB-rifampicin plates for rifampicin resistant (Rifr) mutants. Appropriate dilutions were spread on LB plates to count the total number of viable cells. Plates were incubated at 37°C and counted after 24 h for survival and after 48 h for mutagenesis. Mutation frequency was calculated as the number of mutants per 108 viable cells.
EMS mutagenesis
Reversion to Lac+ was performed as described by Watanabe et al. (1994). Bacteria were grown overnight in E minimal medium to maintain the F' episome. Overnight cultures were adjusted to an OD600 of 0.8 with fresh E medium. A 0.1 ml aliquot of bacterial suspension and the appropriate amount of EMS solution were added to 5 ml of molten MM-top agar and overlayed onto MM-Lac+ plates. Plates were incubated at 37°C for 2 days. For rifampicin resistance mutagenesis, bacteria were cultured overnight as described above and plated using the three-layer method described by Sedgwick and Goodwin (1985). EMS was added to molten top LB and mixed with bacterial suspension as described above. It was then overlayed on LB plates and, after solidification, 2 ml of top LB was added onto the surface. Plates were incubated for 3 h at 37°C and 2 ml of molten top LB containing rifampicin was then overlayed on the top of each plate. Final concentration of EMS was 5 µl/30 ml agar on the plate. Control plates contained DMSO in place of EMS. Lac+ and Rifr mutants were counted after 48 h at 37°C and results are presented as the number of mutants per plate.
Spontaneous mutagenesis in mutator strains
Ten independent cultures of F' carrying strains, inoculated from single colonies into E minimal medium with appropriate antibiotic, were incubated overnight. Samples of 0.1 ml were spread on MM-Lac+ or LB-rifampicin plates for mutagenesis. Aliquots of 0.1 ml of appropriate dilution were spread on LB plates for viable cells. Bacteria were incubated at 37°C. Mutant and viable colonies were counted after 48 and 24 h, respectively. Mutation frequency was calculated as the number of mutants per 108 viable cells. Statistical significance was calculated using two different non-parametric tests: the Kolmogorow–Smirnow and Mann–Whitney U-test. Significance was assigned when two-tailed P values were 
0.05.
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Results |
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Effect of isfA mutation on transitions in the lacZ gene and forward mutations induced by UV light
UV light is known to induce primarily base substitutions (75%), mostly G:C
A:T and A:TG:C transitions, which are SOS-dependent (Miller, 1985; Schaaper et al., 1987; Friedberg et al., 1995). We studied the effect of the isfA mutation on these UV-induced transitions. The level of UV-induced transversions in the lacZ gene was too low to study the effect of the isfA mutation. Results for isf+ and isfA are presented in Table II. The high sensitivity of the isfA mutant to UV irradiation (Bebenek and Pietrzykowska, 1995) led us to measure the mutation frequency in isf+ and isfA strains after irradiation with equal UV doses (10 J/m2) or with doses giving comparable survival in both types of strains (5 J/m2 for isfA and 20 J/m2 for isf+). Mutation frequencies at UV doses of 5 J/m2 for isf+ and of 20 J/m2 for isfA were not determined. The surviving fraction of isfA cells after 20 J/m2 would be well below 0.001, thus the calculated mutation frequency would be unreliable. On the other hand, a dose of 5 J/m2 for the wild-type strain is too low to observe any increase in mutation frequency so the inhibitory effect of isfA could not be seen.
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The results presented in Table II
show that in control strains the frequencies of the two transitions increase with UV dose, as described by Cupples and Miller (1989). The antimutagenic effect of the isfA mutation can be seen for both transitions and forward mutations to rifampicin resistance. Since G:CA:T and A:TG:C transitions arise after UV irradiation in an SOS-dependent manner, the results suggest that the antimutator activity of the isfA mutation is due to its preventing SOS induction.
Effect of isfA mutation on G:CA:T transitions in the lacZ gene and forward mutations induced by EMS
EMS is an alkylating agent known to modify mainly guanine in DNA, to give O6-ethylguanine. Mutations arise during DNA replication by mispairing of O6-ethylguanine with thymine, leading to G:CA:T transitions. The EMS-induced mutagenic pathway does not require SOS functions (Schendel and Defais, 1980; Todd et al., 1981; Kato et al., 1982). The results presented in Figure 1 show that the isfA mutation has no effect on EMS-induced G:CA:T transitions in the lacZ gene, although it did affect G:CA:T transitions induced by UV irradiation in the same strain. The results further indicate that the antimutagenic activity of the isfA mutation is specific for the SOS-dependent mutagenic pathway and not for base substitution. A small decrease in the number of rifampicin-resistant mutants (Figure 1) in the isfA strain suggests that some of the premutagenic lesions induced by EMS (e.g. AP sites) could be converted to mutations by an SOS-dependent pathway.
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Effect of isfA mutation on the mutator activity in recA730, mutL and the double mutant recA730 mutL
A high level of spontaneous mutations in mutator strains may result from different cellular mechanisms. In the recA730 strain, mutations result from constitutive expression of the SOS system (Witkin et al., 1982
; Lavery and Kowalczykowski, 1992). In the mutL mutator, deficient in mismatch repair, mutations, mainly transitions, arise from replication errors not corrected by this system (Schaaper and Dunn, 1987; Friedberg et al., 1995). To study the antimutagenic specificity of the isfA mutation for base substitutions introduced into DNA by different mutagenic mechanisms, we analysed mutation frequencies of the two transitions and four transversions in the lacZ gene arising spontaneously in the recA730, mutL and in recA730 mutL strains carrying the isfA mutation.
Results obtained for transitions and three transversions are presented in Table III (data for the G:CC:G transversion are not shown because of an extremely low number of mutants observed). In the recA730 strains A:TT:A, A:TC:G and G:CT:A transversions are the main classes of mutations (column 3), as shown previously by Watanabe-Akanuma et al. (1997) and Fijalkowska et al. (1997). The isfA mutation decreases these transversions (column 4) to the level observed in rec+ strains (columns 1 and 2). On the other hand, a deficiency in mismatch repair in the mutL strain leads to a large increase of only G:CA:T and A:TG:C transitions. These transitions are not affected by the isfA mutation (columns 5 and 6), indicating that replication errors introduced during normal DNA replication in a rec+ background are not subject to inhibition by the isfA mutation.
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In the double mutant recA730 mutL both transitions and transversions are enhanced (column 7) compared with the single mutants recA730 or mutL. The frequencies of A:T
T:A, A:TC:G and G:CT:A transversions in recA730 mutL are 2- to 6-fold higher compared with recA730 (cf. columns 3 and 7), showing that transversions in the recA730 mutant are partially removed by mismatch repair. The efficiency of mismatch repair in recA730 is higher for G:CT:A and A:TC:G than for A:TT:A transversions. In mutL strains, transversions are very rare but in the double mutant recA730 mutL the frequencies increase 15- to 125-fold, indicating that they are generated specifically by the recA730 mutation. The isfA mutation in the recA730 mutL background leads to >95% inhibition of A:TT:A and A:TC:G and 85% inhibition of G:CT:A transversions (columns 7 and 8). Frequencies of G:CA:T and A:TG:C transitions in recA730 mutL are 2- and 10-fold higher, respectively, than in mutL, indicating that 50% of G:CA:T and 90% of A:TG:C transitions in the double mutant originate from the SOS mutator pathway. The presence of the isfA mutation reduces the levels of both types of transitions (columns 7 and 8) in recA730 mutL to that observed in mutL (column 6), indicating that it affects only those transitions generated by the recA730 mutation. A similar effect of the isfA mutation can be seen for mutagenesis to rifampicin resistance in all reported strains. The isfA mutation reduces the frequency of Rifr mutants in the recA730 strain to the level observed in the rec+ control strain, but it does not affect the frequency of mutations due to a deficiency of mismatch repair in the mutL strain. In the double mutant recA730 mutL, the isfA mutation reduces the frequency of Rifr mutants to the level observed in the mutL strain, indicating that only mutations generated by a recA730-dependent pathway are affected.
Since the antimutator effect of the isfA mutation in the recA730 mutL background can be observed for transitions, as well as transversions and forward mutations, but not for transitions in the mutL background, we propose that isfA activity is not specific for any kind of base substitution, but is specific for the SOS-dependent mutagenic pathway active in the recA730 strain.
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Discussion |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
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We have previously shown that the isfA mutation inhibits SOS-dependent phenomena, including UV- and MMS-induced mutagenesis and mutator activity in the recA730 strain, but does not affect EMS-induced mutagenesis (Bebenek and Pietrzykowska, 1995
, 1996), known to be SOS-independent (Schendel and Defais, 1980; Todd et al., 1981; Kato et al., 1982).
The present study poses the question as to whether the isfA antimutagenic activity is specific to some types of base substitutions, transitions or transversions or specifically inhibits the SOS-dependent mutagenic pathway. We analysed the antimutagenic activity of the isfA mutation, using the lacZ system (Cupples and Miller, 1989) in different genetic backgrounds or using different mutagens. Our results lead to the conclusion that the isfA mutation does not inhibit transitions generated as errors of DNA replication, either spontaneous, as observed in the mutL strain, or induced by EMS. It does, however, inhibit the same transitions when induced by UV light. Since in all cases the same defined G:CA:T transition in the lacZ gene was studied and the only difference was the mutagenic pathway by which mutations were generated, it may safely be concluded that the isfA antimutagenic activity is directed towards the SOS-dependent mutagenic pathway but not to any particular base substitutions.
This conclusion is further supported by the experiments with the recA730 and recA730 mutL strains. In the recA730 mutator strain the majority of mutations are transversions, which are SOS- and UmuD'C-dependent (Table III; Watanabe-Akanuma et al., 1997). The isfA mutation efficiently inhibits practically all transversions in the recA730 strain, most probably due to inhibition of processing of UmuD to UmuD', as shown by Bebenek and Pietrzykowska (1996). In contrast to the transversions, transitions are induced in recA730 only at a very low level (Table III; Fijalkowska et al., 1997; Watanabe-Akanuma et al., 1997). However, the deficiency in mismatch repair in the recA730 mutL strain leads to the appearance of G:CA:T and A:TG:C transitions, indicating that most of them are efficiently corrected by the mutHLS system. The same effect of mutL in the recA730 strain has also been reported by Fijalkowska et al. (1997).
It is interesting to compare the effect of the isfA mutation on the G:CA:T and A:TG:C transitions in the mutL and recA730 mutL strains. While isfA does not affect these transitions in the mutL single mutant, it reduces them in the double mutant to the level observed in mutL, showing that G:CA:T and A:TG:C transitions in recA730 mutL result from two different mutagenic pathways, SOS-dependent and SOS-independent. This is in agreement with the model proposed by Fijalkowska et al. (1997) for the mechanism of mutagenesis occurring in the recA730 strain. These authors postulate the existence of two replicative systems in the recA730 strain. One is the normal DNA polymerase III holoenzyme and the other is the error-prone DNA polymerase III complex modified by the RecA* and UmuD'C proteins (Woodgate et al., 1989; Echols and Goodman, 1991; Slater and Maurer, 1991; Rajagopolan et al., 1992; Woodgate and Levine, 1996). The isfA mutation most probably affects only the latter replicative complex by inhibiting the processing of UmuD to UmuD' (Bebenek and Pietrzykowska, 1996), which leads to inhibition of the SOS mutator activity in recA730 cells.
It is worth noting that in the recA730 mutL isfA strain, A:TC:G and A:TT:A transversions are inhibited by the isfA mutation with an efficiency >95% while G:CT:A transversions are inhibited less efficiently (~85%). The difference in efficiency of inhibition is statistically significant (P < 0.05) and suggests that ~15% of G:CT:A transversions may be generated by a mutagenic pathway which differs from the RecA*- and UmuD'C-dependent pathway, which is susceptible to inhibition by the isfA mutation. Recently Kim et al. (1997) described a new mutagenic pathway which is SOS-dependent, UmuDC-independent. They showed that overproduction of the dinP/B gene product leads to a high increase in spontaneous mutations, mainly deletions. Among base substitutions only G:CT:A transversions were significantly enhanced. Since we have shown that in recA730 the isfA mutation inhibits only the processing of UmuD to UmuD', but not derepression of din genes (Bebenek and Pietrzykowska, 1996), part of the G:CT:A transversions observed in the double mutant recA730 mutL may arise by the mutagenic pathway described by Kim et al. (1997). Since G:CT:A transversions are efficiently removed by mismatch repair (see Table III), they cannot be seen in the recA730 isfA mismatch-proficient strain.
Our results clearly indicate that the isfA mutation specifically inhibits only the SOS-dependent mutagenic pathway and does not selectively affect any particular base substitution. By studying the effect of the isfA mutation on transitions and transversions in the lacZ gene in different genetic backgrounds, we were able to recognize different mutagenic pathways active in recA730 cells: (i) SOS- and UmuD'C-dependent, inhibited by the isfA mutation; (ii) SOS-independent, not inhibited by the isfA mutation, in which mutations result from errors of DNA replication. The existance of a third possible mutagenic pathway in recA730, which is SOS-dependent but not inhibited by isfA, is also suggested by the results. This could be an SOS-dependent, UmuD'C-independent mutagenic pathway, involving the DinP/B protein recently reported by Kim et al. (1997).
Taken together, our overall results suggest that the isfA mutation may be a useful tool in the identification of the mechanism(s) by which mutations arise, SOS-dependent or SOS-independent.
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Acknowledgments |
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We thank Prof. Jeffrey H.Miller (University of California, Los Angeles, CA) for providing bacterial strains CC101–CC106 and Prof. Roel M.Schaaper (National Institute of Environmental Health Sciences, Research Triangle Park) for providing (via I.Fijalkowska) strains KA796, NR11531 and NR9559. We thank Drs Iwona J.Fijalkowska and Piotr Jonczyk for helpful discussion and Prof. David Shugar for critical reading of the manuscript. This study was supported in part by grant no. 235/PO4/97/12 from the Committee for Scientific Research, Poland.
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Notes |
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1 To whom correspondence should be addressed. Tel: +48 658 47 19; Fax: +48 39 12 16 23; Email: magfel{at}ibb.waw.pl
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References |
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Bebenek,A. and Pietrzykowska,I. (1995) A new mutation in Escherichia coli K12, isfA, which is responsible for inhibition of SOS functions. Mol. Gen. Genet., 248, 103–113.[Web of Science][Medline]
Bebenek,A and. Pietrzykowska,I. (1996) The isfA mutation inhibits mutator activity and processing of UmuD protein in Escherichia coli recA730 strain. Mol. Gen. Genet., 250, 674–680.[Web of Science][Medline]
Burckhardt,S.E., Woodgate,R., Scheuermann,R.H. and Echols,H. (1988) UmuD mutagenesis protein of Escherichia coli: overproduction, purification, and cleavage by RecA. Proc. Natl Acad. Sci. USA, 85, 1811–1815.
Castellazzi,M., George,J. and Buttin,G. (1972) Prophage induction and cell division in E.coli. I. Further characterization of a thermosensitive mutation tif-1 whose expression mimics the effects of UV irradiation. Mol. Gen. Genet., 119, 139–152.[Web of Science][Medline]
Cupples,C.G. and Miller,J.H. (1989) A set of lacZ mutations in Escherichia coli that allow rapid detection of each of the six base substitutions. Proc. Natl Acad. Sci. USA, 86, 5345–5349.
Echols,H. and Goodman,M.F. (1991) Fidelity mechanisms in DNA replication. Annu. Rev. Biochem., 60, 477–511.[Web of Science][Medline]
Ennis,D.G., Fisher,B., Edmiston,S. and Mount,D.W. (1985) Dual role of Escherichia coli RecA protein in SOS mutagenesis. Proc. Natl Acad. Sci. USA, 82, 3325–3329.
Ennis,D.G., Levine,A.S., Koch,W.H. and Woodgate,R. (1995) Analysis of recA mutants with altered SOS functions. Mutat. Res., 336, 39–48.[Web of Science][Medline]
Fijalkowska,I.J. and Schaaper,R.M. (1995) Effects of Escherichia coli dnaE antimutator alleles in a proofreading-deficient mutD5 strain. J. Bacteriol., 177, 5979–5986.
Fijalkowska,I.J., Dunn,R.L. and Schaaper,R.M. (1997) Genetic requirements and mutational specificity of the Escherichia coli SOS mutator activity. J. Bacteriol., 179, 7435–7445.
Friedberg,E.C., Walker,G.C. and Siede,W. (1995) DNA Repair and Mutagenesis. American Society for Microbiology Press, Washington, DC.
Kato,T., Ise,T. and Shinagawa,H. (1982) Mutational specificity of the umuC mediated mutagenesis in Escherichia coli. Biochimie, 64, 731–733.[Medline]
Kim,S., Maenhaut-Michel,G., Yamada,M., Yamamoto,Y., Matsui,K., Sofuni,T. Nohmi,T. and Ohmori,H. (1997) Multiple pathways for SOS-induced mutagenesis in Escherichia coli: an overexpression of dinB/dinP results in strongly enhancing mutagenesis in the absence of any exogenous treatment to damage DNA. Proc. Natl Acad. Sci. USA, 94, 13792–13797.
Lavery,P.E. and Kowalczykowski,S.C. (1992) Biochemical basis of the constitutive repressor cleavage activity of recA730 protein. A comparison to recA441 and recA803 proteins. J. Biol. Chem., 267, 20648–20658.
Little,J.W. (1991) Mechanism of specific LexA cleavage: autodigestion and the role of RecA coprotease. Biochimie, 73, 411–422.[Medline]
Miller,J.H. (1972) Experiments in Molecular Genetics. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
Miller,J.H. (1985) Mutagenic specificity of ultraviolet light. J. Mol. Biol., 182, 45–68.[Web of Science][Medline]
Modrich,P. (1991) Mechanisms and biological effects of mismatch repair. Annu. Rev. Genet., 25, 229–253.[Web of Science][Medline]
Modrich,P. and Lahue,R. (1996) Mismatch repair in replication fidelity, genetic recombination, and cancer biology. Annu. Rev. Biochem., 65, 101–133.[Web of Science][Medline]
Nohmi,T., Battista,J.R., Dodson,L.A. and Walker,G.C. (1988) RecA-mediated cleavage activates UmuD for mutagenesis: mechanistic relationship between transcriptional derepression and post-translational activation. Proc. Natl Acad. Sci. USA, 85, 967–978.
Rajagopolan,M., Lu,C., Woodgate,R., O'Donnell,M., Goodman,M.F.and Echols,H. (1992) Activity of the purified mutagenesis proteins UmuC, UmuD', and RecA in replicative bypass of an abasic DNA lesion by DNA polymerase III. Proc. Natl Acad. Sci. USA, 89, 10777–10781.
Salles,B. and Defais,M. (1984) Signal of induction of recA protein in E.coli. Mutat Res., 131, 53–59.[Web of Science][Medline]
Sanssafar,M. and Roberts,J.W. (1990) Nature of the SOS-inducing signal in Escherichia coli: the involvment of DNA replication. J. Mol. Biol, 212, 79–96.[Web of Science][Medline]
Schaaper,R.M. and Dunn,R.L. (1987) Spectra of spontaneous mutations in Escherichia coli strains deffective in mismatch correction: the nature of in vivo DNA replication errors. Proc. Natl Acad. Sci. USA, 84, 6220–6224.
Schaaper,R.M., Danforth,B.N. and Glickman,B.W. (1985) Rapid repeated cloning of mutant lac repressor genes. Gene, 39, 181–189.[Web of Science][Medline]
Schaaper,R.M., Dunn,R.L. and Glickman,B.W. (1987) Mechanisms of ultraviolet-induced mutation. Mutational spectra in the Escherichia coli lacI gene for a wild-type and an excision-repair-deficient strain. J. Mol. Biol., 198, 187–202.[Web of Science][Medline]
Schendel,P.F.and Defais,M. (1980) The role of umuC gene product in mutagenesis by simple alkylating agents. Mol. Gen. Genet., 177, 661–665.[Web of Science][Medline]
Sedgwick,S.G. and Goodwin,P.A. (1985) Difference in mutagenic and recombinational DNA repair in enterobacteria. Proc. Natl Acad. Sci. USA, 82, 4172–4176.
Shinagawa,H., Iwasaki,H., Kato,T. and Nakata,A. (1988) RecA protein-dependent cleavage of UmuD protein and SOS mutagenesis. Proc. Natl Acad. Sci. USA, 85, 1806–1810.
Slater,S.C. and Maurer,R. (1991) Requirements for bypass of UV-induced lesions in single-stranded DNA of bacteriophage 
X174 in Salmonella typhimurium. Proc. Natl Acad. Sci. USA, 88, 1251–1255.
Sweasy,J.B., Witkin,E.M., Sinha,N. and Roegner-Maniscalco,V. (1990) RecA protein of Escherichia coli has a third essential role in SOS mutator activity. J. Bacteriol., 172, 3030–3036.
Todd,P.A., Brouwer,J. and Glickman,B.W. (1981) Influence of DNA repair deficiences on MMS- and EMS-induced mutagenesis in Escherichia coli K12. Mutat. Res., 82, 239–250.[Web of Science][Medline]
Vogel,H.L. and Bonner,D.M. (1956) Acetylornithinase of Escherichia coli: partial purification and some properties. J. Biol. Chem., 218, 97–106.
Wang,W.B. and Tessman,E.S. (1986) Location of functional regions of the Escherichia coli RecA protein by DNA sequence analysis of RecA protease-constitutive mutants. J. Bacteriol., 168, 901–910.
Watanabe,M., Nohmi,T.and Ohta,T. (1994) Effects of the umuDC, mucAB and samAB operons on the mutational specificity of chemical mutagenesis in Escherichia coli: I. Frameshift mutagenesis. Mutat. Res., 314, 27–37.[Web of Science][Medline]
Watanabe-Akanuma,M., Woodgate,R and Ohta,T. (1997) Enhanced generation of A:TT:A transversions in recA730lexA(Def) mutant of Escherichia coli. Mutat. Res., 373, 61–66.[Web of Science][Medline]
Witkin,E.M. and Kogoma,T. (1984) Involvment of the activated form of RecA protein in SOS mutagenesis and stable DNA replication in Escherichia coli. Proc. Natl Acad. Sci. USA, 81, 7539–7543.
Witkin,E.M., McCall,J.O., Volkert,M.R. and Wermundsen,I.E. (1982) Constitutive expression of SOS functions and modulation of mutagenesis resulting from resolution of genetic instability at or near the recA locus of Escherichia coli. Mol. Gen. Genet., 185, 43–50.[Web of Science][Medline]
Woodgate,R. and Ennis,D.G. (1991) Levels of chromosomally encoded Umu proteins and requirements for in vivo UmuD cleavage. Mol. Gen. Genet., 229, 10–16.[Web of Science][Medline]
Woodgate,R. and Levine,A.S. (1996) Damage inducible mutagenesis: recent insights into the activities of the Umu family of mutagenesis proteins. Cancer Surv., 28, 117–140.[Web of Science][Medline]
Woodgate,R., Rajagopolan,M., Lu,C. and Echols,H. (1989) UmuC mutagenesis protein of Escherichia coli: purification and interaction with UmuD and UmuD'. Proc. Natl Acad. Sci. USA, 86, 7301–7305.
Received on September 3, 1998; accepted on December 10, 1998.
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