Role of mismatch repair in the Escherichia coli UVM response

Murphy, Holly S.; Palejwala, Vaseem A.; Rahman, M. Sayeedur; Dunman, Paul M.; Wang, G; Humayun, M. Zafri

doi:10.1128/jb.178.23.6651-6657.1996

Cited by 9 publications

(14 citation statements)

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“…Subsequent work confirmed that UVM (for UV modulation of mutagenesis) response did not require any of the genes known to be required for SOS mutagenesis ( Palejwala et al ., 1995 ). UVM does not appear to arise from a depletion of known mismatch repair activities ( Murphy et al ., 1996 ). The preponderance of evidence indicates that the UVM effect results from a transient alteration of the DNA replication environment.…”

Section: The Uvm Responsementioning

confidence: 99%

SOS and Mayday: multiple inducible mutagenic pathways in Escherichia coli

Humayun

1998

Molecular Microbiology

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SummaryEnvironmental and physiological stress conditions can transiently alter the fidelity of DNA replication. The DNA damage-mediated SOS response in Escherichia coli is the best-known example of such an 'inducible mutagenesis' or 'transient mutator' pathway. Emerging evidence suggests the existence of a number of other stress-inducible pathways that also affect the fidelity of replication. Among the more provocative recent findings are UVM, an SOS-independent damageinducible mutagenic pathway, and a new recA-dependent but umuD/C-independent pathway that appears to be provoked by translational stress. These findings alter our view of inducible mutagenesis, and anticipate the existence of previously unrecognized links between protein synthesis and DNA replication. The SOS hypothesisThe idea of inducible error-prone replication evolved from observations such as enhanced mutagenesis of UV-irradiated lambda phage in UV-irradiated cells compared with unirradiated cells. A unifying mechanism that tightly links base insertion opposite a DNA lesion and lesion bypass, as proposed by the SOS hypothesis, is both logical and simple. Experimental evidence supporting elements of the SOS hypothesis came from a large number of laboratories, and the hypothesis in turn provided the theoretical framework for rapid advances in the identification and characterization of the SOS regulon (for review see Friedberg et al., 1995). According to current interpretation, unrepaired bulky or non-instructive DNA damage blocks DNA replication and can be lethal unless specific proteins are induced to stimulate DNA repair and to restore replication past blocked sites. The expression of these proteins is normally repressed by the binding of the LexA protein to the promoter. An SOS-inducing signal is generated when DNA replication is arrested at sites of damage. It is believed that aborted replication exposes single-stranded DNA at replication forks to binding by the RecA protein. The DNA-bound RecA protein undergoes a conformational transition to RecA * , the SOS-active form of the RecA protein.

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Section: The Uvm Responsementioning

confidence: 99%

SOS and Mayday: multiple inducible mutagenic pathways in Escherichia coli

Humayun

1998

Molecular Microbiology

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“…Although base-or nucleotideexcision repair is probably after translesion synthesis, such repair would be futile because the mutation has already been fixed. Hypothetical postreplicative mismatch-repair mechanisms can account for the UVM effect Wang et al, 1995), but our data so far do not reveal a requirement for any of the known E. coli mismatch-repair activities for UVM (Murphy et al, 1996). On the other hand, a previously unrecognized (hypothetical) non-excisive repair mechanism can account for UVM in the following scenario.…”

Section: Discussionmentioning

confidence: 43%

“…UVM has been shown to be distinct from known DNA damageinducible E. coli responses, including the SOS response , the adaptive response to alkylation damage , as well as cellular responses to oxidative stress mediated by the oxyR gene . The UVM response does not require DNA polymerase I or DNA polymerase II , and cannot be readily accounted for by simple repair-depletion models (Murphy et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Effect of UVM induction on mutation fixation at non‐pairing and mispairing DNA lesions

Rahman

Dunman

Wang

et al. 1996

Molecular Microbiology

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Mutation fixation at an ethenocytosine (epsilon C) residue borne on transfected M13 single-stranded DNA is significantly enhanced in response to pretreatment of Escherichia coli cells with UV, alkylating agents or hydrogen peroxide, a phenomenon that we have called UVM for UV modulation of mutagenesis. The UVM response does not require the E. coli SOS or adaptive responses, and is observed in cells defective for oxyR, an oxidative DNA damage-responsive regulatory gene. UVM may represent either a novel DNA-repair phenomenon, or an unrecognized feature of DNA replication in damaged cells that affects a specific class of non-coding DNA lesions. To explore the range of DNA lesions subject to the UVM effect, we have examined mutation fixation at 3,N4-ethenocytosine and 1,N6-ethenoadenine, as well as at O6-methylguanine (O6mG). M13 viral single-stranded DNA constructs bearing a single mutagenic lesion at a specific site were transfected into cells pretreated with UV or 1-methyl-3-nitro-1-nitroso-guanidine (MNNG). Survival of transfected viral DNA was measured as transfection efficiency, and mutagenesis at the lesion site was analysed by a quantitative multiplex sequence analysis technology. The results suggest that the UVM effect modulates mutagenesis at the two etheno lesions, but does not appear to significantly affect mutagenesis at O6mG. Because the modulation of mutagenesis is observed in cells incapable of the SOS response, these data are consistent with the notion that UVM may represent a previously unrecognized DNA damage-inducible response that affects the fidelity of DNA replication at certain mutagenic lesions in Escherichia coli.

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“…This finding has been interpreted to mean that induced SOS proteins are required only under specific circumstances to overcome the polymerase cycling forced by normal editing at lesion sites. We have noted previously that the preponderance of evidence indicates that the UVM response is mediated through an alteration of DNA replication (13). Mutation fixation at εC residues was reported to be increased in mutD5 cells to the same extent as in UV-irradiated cells (11).…”

Section: Discussionmentioning

confidence: 97%

“…UVM appears to significantly affect mutagenesis at class 2 noninstructive lesions such as εC and possibly 1,N 6 -ethenoadenine but not at mispairing lesions such as O 6 -methylguanine (19). The mechanisms underlying the UVM response are not known, but the prepon-derance of evidence points to the transient induction of an error-prone replication activity (12)(13)(14)17).…”

mentioning

confidence: 99%

SOS and UVM Pathways Have Lesion-Specific Additive and Competing Effects on Mutation Fixation at Replication-Blocking DNA Lesions

Rahman

Humayun

1999

J Bacteriol

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Escherichia coli cells have multiple mutagenic pathways that are induced in response to environmental and physiological stimuli. Unlike the well-investigated classical SOS response, little is known about newly recognized pathways such as the UVM (UV modulation of mutagenesis) response. In this study, we compared the contributions of the SOS and UVM pathways on mutation fixation at two representative noninstructive DNA lesions: 3, N4-ethenocytosine (ɛC) and abasic (AP) sites. Because both SOS and UVM responses are induced by DNA damage, and defined UVM-defective E. colistrains are not yet available, we first constructed strains in which expression of the SOS mutagenesis proteins UmuD′ and UmuC (and also RecA in some cases) is uncoupled from DNA damage by being placed under the control of a heterologous lac-derived promoter. M13 single-stranded viral DNA bearing site-specific lesions was transfected into cells induced for the SOS or UVM pathway. Survival effects were determined from transfection efficiency, and mutation fixation at the lesion was analyzed by a quantitative multiplex sequence analysis procedure. Our results suggest that induction of the SOS pathway can independently elevate mutagenesis at both lesions, whereas the UVM pathway significantly elevates mutagenesis at ɛC in an SOS-independent fashion and at AP sites in an SOS-dependent fashion. Although mutagenesis at ɛC appears to be elevated by the induction of either the SOS or the UVM pathway, the mutational specificity profiles for ɛC under SOS and UVM pathways are distinct. Interestingly, when both pathways are active, the UVM effect appears to predominate over the SOS effect on mutagenesis at ɛC, but the total mutation frequency is significantly increased over that observed when each pathway is individually induced. These observations suggest that the UVM response affects mutagenesis not only at class 2 noninstructive lesions (ɛC) but also at classical SOS-dependent (class 1) lesions such as AP sites. Our results add new layers of complexity to inducible mutagenic phenomena: DNA damage activates multiple pathways that have lesion-specific additive as well as suppressive effects on mutation fixation, and some of these pathways are not directly regulated by the SOS genetic network.

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Role of mismatch repair in the Escherichia coli UVM response

Cited by 9 publications

References 50 publications

SOS and Mayday: multiple inducible mutagenic pathways in Escherichia coli

SOS and Mayday: multiple inducible mutagenic pathways in Escherichia coli

Effect of UVM induction on mutation fixation at non‐pairing and mispairing DNA lesions

SOS and UVM Pathways Have Lesion-Specific Additive and Competing Effects on Mutation Fixation at Replication-Blocking DNA Lesions

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