Recognition of the DNA helix stabilizing anthramycin-N2 guanine adduct by UVRABC nuclease

Walter, Ronald B.; Pierce, James; Case, Roger; Tang, Moon‐shong

doi:10.1016/0022-2836(88)90119-2

Cited by 39 publications

(22 citation statements)

References 20 publications

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“…In the former case, no effect of supercoiling was detected (Fig. 5), whereas in the latter case, it is the relaxed modified DNA that is cut more efficiently than the supercoiled DNA (19).…”

Section: Resultsmentioning

confidence: 92%

The noncovalent complex between DNA and the bifunctional intercalator ditercalinium is a substrate for the UvrABC endonuclease of Escherichia coli.

Lambert

Jones²,

Roques³

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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We have demonstrated that the noncovalent complex formed between DNA and an antitumor bifunctional intercalator, ditercalinium, is recognized in vitro as bulky covalent DNA lesions by the purified Escherichia coli UvrABC endonuclease. It was established that no covalent drug-DNA adduct was formed during the incubation ofthe drug with DNA or during subsequent incubation with the UvrAB proteins. The nucleoprotein-ditercalinium complexes appear different from those generated by repair of pyrimidine dimers. The UvrA protein is able to form a stable complex with ditercaliniumintercalated DNA in the presence of ATP, whereas both UvrA and UvrB proteins are required to form a stable complex with pyrimidine dimer-containing DNA. The apparent half-life of the UvrA-and UvrAB-ditercalinium-DNA complexes following removal of free ditercalinium is 5 min. However, if the free ditercalinium concentration is maintained to allow the intercalation of one molecule of ditercalinium per 3000 base pairs, the half-life of the UvrA-or UvrAB-ditercalinium-DNA complex is 50 min, comparable to that of the complex of UvrAB proteins formed with pyrimidine dimer-containing DNA.UvrABC endonuclease incises ditercalinium-intercalated DNA as efficiently as pyrimidine dimer-containing DNA. However, unlike repair of pyrimidine diners, the incision reaction is strongly favored by the supercoiling of the DNA substrate. Because UvrA-or UvrAB-ditercalinium-DNA complexes can be formed with relaxed DNA without leading to a subsequent incision reaction, these apparently dead-end nucleoprotein complexes may become lesions in themselves resulting in the cytotoxicity of ditercalinium. Our results show that binding of excision repair proteins to a noncovalent DNA-ligand complex may lead to cell toxicity.

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“…In the former case, no effect of supercoiling was detected (Fig. 5), whereas in the latter case, it is the relaxed modified DNA that is cut more efficiently than the supercoiled DNA (19).…”

Section: Resultsmentioning

confidence: 92%

The noncovalent complex between DNA and the bifunctional intercalator ditercalinium is a substrate for the UvrABC endonuclease of Escherichia coli.

Lambert

Jones²,

Roques³

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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“…These DNase I footprinting results are consistent with the UvrABC nuclease system incision efficiency for these two BPDE-DNA adducts. It has been suggested that the UvrABC nuclease complex generally recognizes a localized DNA helix alteration including bending, kinking, and unwinding rather than a specific modified nucleotide [Van Houten et al, 1986;Walter et al, 1988;and reviewed in Van Houten (1990)l. The BPDE-DNA adducts have different effects on the thermostability of 1 lmer duplexes such that the T m of the unmodified 1 lmer is 50.5 OC, whereas the Tm' S for the (+)-and (-)-trans isomers are 40 and 43.2 OC, respectively (Ya et al, 1994).…”

Section: Bpde-dna Adduct Recognition and Repair: Structure-function Rmentioning

confidence: 99%

Interaction of the UvrABC Nuclease System with a DNA Duplex Containing a Single Stereoisomer of dG-(+)- or dG-(-)-anti-BPDE

Zou

Liu

Geacintov³

et al. 1995

Biochemistry

128

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Oligonucleotides containing site-specifically-modified N2-guanine (+)-trans-, (-)-trans-, (+)-cis-, and (-)-cis-BPDE adducts were ligated into 50-base-pair DNA fragments. These substrates were used in reactions with the Escherichia coli UvrABC nuclease system. The interaction of the UvrA2 and UvrA2B complexes with these four stereoisomers was probed using DNase I footprinting and gel mobility shift assays. DNase I digestion of substrates containing each stereoisomer of BPDE displayed a unique pattern which was consistent with the known structure of these DNA adducts. UvrA and UvrA2B appeared to interact very similarly with all four substrates. Binding of UvrA2 to these substrates produced a 33-bp footprint, and the UvrB--DNA complex resulted in footprint of 24 bp. The UvrABC nuclease system produced bimodal incisions at the eighth phosphate 5' and the fifth, sixth, or seventh phosphate 3' to the modified guanine. The variation of the 3' incision site was linked to the stereochemistry and orientation of the BPDE adduct. For example, the 3' incision of the 50-bp duplex containing (-)-trans-BPDE-N2-guanine was inhibited at the fifth phosphate. UvrABC nuclease incision kinetics revealed a hierarchy of specificity. The intercalative cis isomers were incised more efficiently than the corresponding trans isomers which lie in the minor groove. The (+) enantiomers were incised more efficiently than the (-) form for both cis and trans isomers. These observations reveal that UvrABC nuclease recognition and incision are directly influenced by the conformation of the DNA adduct.

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“…If this is the case, then it is expected that the UvrABC incision of an ICL dG-MC-dG lesion will be different since this type of lesion does not cause DNA kinking or bending and either DNA strand can wrap around UvrB molecules. The signal for UvrA binding at this ICL lesion probably comes from the changing helix fluidity caused by this type of lesion (39). Our gel retardation results indicate that UvrA remains bound to the MC-modified DNA fragments after addition of UvrB and UvrC proteins; this differs from the results of van Houten et al .…”

Section: Discussionmentioning

confidence: 99%

Repair of mitomycin C mono- and interstrand cross-linked DNA adducts by UvrABC: a new model

Weng

Zheng

Jasti

et al. 2010

Nucleic Acids Research

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Mitomycin C induces both MC-mono-dG and cross-linked dG-adducts in vivo. Interstrand cross-linked (ICL) dG-MC-dG-DNA adducts can prevent strand separation. In Escherichia coli cells, UvrABC repairs ICL lesions that cause DNA bending. The mechanisms and consequences of NER of ICL dG-MC-dG lesions that do not induce DNA bending remain unclear. Using DNA fragments containing a MC-mono-dG or an ICL dG-MC-dG adduct, we found (i) UvrABC incises only at the strand containing MC-mono-dG adducts; (ii) UvrABC makes three types of incisions on an ICL dG-MC-dG adduct: type 1, a single 5′ incision on 1 strand and a 3′ incision on the other; type 2, dual incisions on 1 strand and a single incision on the other; and type 3, dual incisions on both strands; and (iii) the cutting kinetics of type 3 is significantly faster than type 1 and type 2, and all of 3 types of cutting result in producing DSB. We found that UvrA, UvrA + UvrB and UvrA + UvrB + UvrC bind to MC-modified DNA specifically, and we did not detect any UvrB- and UvrB + UvrC–DNA complexes. Our findings challenge the current UvrABC incision model. We propose that DSBs resulted from NER of ICL dG-MC-dG adducts contribute to MC antitumor activity and mutations.

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Recognition of the DNA helix stabilizing anthramycin-N2 guanine adduct by UVRABC nuclease

Cited by 39 publications

References 20 publications

The noncovalent complex between DNA and the bifunctional intercalator ditercalinium is a substrate for the UvrABC endonuclease of Escherichia coli.

The noncovalent complex between DNA and the bifunctional intercalator ditercalinium is a substrate for the UvrABC endonuclease of Escherichia coli.

Interaction of the UvrABC Nuclease System with a DNA Duplex Containing a Single Stereoisomer of dG-(+)- or dG-(-)-anti-BPDE

Repair of mitomycin C mono- and interstrand cross-linked DNA adducts by UvrABC: a new model

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