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Effect of UVM induction on mutation fixation at non‐pairing and mispairing DNA lesions
Author(s) -
Sayeedur Rahman M.,
Dunman Paul M.,
Wang Ge,
Murphy Holly S.,
Zafri Humayun M.
Publication year - 1996
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1046/j.1365-2958.1996.d01-1723.x
Subject(s) - mutagenesis , biology , dna damage , dna repair , dna , microbiology and biotechnology , transfection , sos response , mutation , replication protein a , dna replication , mutant , gene , genetics , dna binding protein , transcription factor
Mutation fixation at an ethenocytosine (εC) 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, N 4 ‐ethenocytosine and 1, N 6 ‐ethenoadenine, as well as at O 6 ‐methylguanine (O 6 mG). 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‐nitrosoguanidine (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 O 6 mG. 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 .