Recognition of mitomycin C-DNA monoadducts by UVRABC nuclease

Kohn, Harold; Li, Ven Shun; Tang, Moon Shong

doi:10.1021/ja00040a003

Cited by 39 publications

(56 citation statements)

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“…To test this possibility the 61-bp DNA fragments containing a site-specific MC-mono-dG adduct were 5′-end- 32 P labeled at either the MC-adduct strands (substrate 1) or the non-adducted strands as shown in Figure 1B, and then reacted with UvrABC nuclease for different time periods. The results in Figure 2A show that UvrABC incises the MC-mono-dG-containing strands as a function of incubation time and incisions mainly occur at 7 nt with minor incisions 8 and 9 nt, 5′ to the MC-dG; these results are consistent with previous findings (10,21). In contrast, UvrABC does not incise the complementary strands that do not contain an MC-mono-dG adduct even after a 60-min incubation period (Figure 2B ) .…”

Section: Resultssupporting

confidence: 92%

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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Section: Resultssupporting

confidence: 92%

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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“…The densitometric data indicated that both the 5′ and 3′ nearest neighbor bases surrounding the guanine site affect it’s susceptibility to drug modification and that MM lesions occurred predominantly at 5′CG sequences. [100] Phillips, White, and Cullinane implemented an in vitro transcription assay exhibiting blockage of transcription by E. coli RNA polymerase at specific DNA sites when mitomycin C was reduced by xanthine oxidase/NADH, that showed selectivity for XpC sequences of the non-coding strand, corresponding to G selectivity of the coding strand. [101] Through experiments in the Hopkins lab involving sequence-random cleavage of MMC cross-linked DNA, the sequence specificity of the cross links was determined at single nucleotide resolution to be at the G of 5′- d(CG) in strong preference to 5′-d(GC).…”

Section: Biochemistrymentioning

confidence: 99%

Mitomycinoid Alkaloids: Mechanism of Action, Biosynthesis, Total Syntheses, and Synthetic Approaches

et al. 2013

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Section: Introductionmentioning

confidence: 98%

“…Monoalkylation appears preferentially at 5'-CG (19)(20)(21) and to a lesser extent 5'-GG sequences (19)(20)(21). It has also been demonstrated that the 3'-base has a relatively modulating effect on the guanine reactivity (20,21 ). Some authors (19,21) proposed the high specificity of 5'-CG sequence as the result of the stabilization of the monofunctional adduct through an H-bond between the C 10 -0 atom of activated mitomycin C and the 2NH 2 group of the guanine residue of the complementary strand.…”

Section: Introductionmentioning

confidence: 99%

Distortion After Monofunctional Alkylation by Mitomycin C of a Dodecamer Containing its Major Binding Site

Berthelier¹,

Laigle²,

Jollès³

et al. 1995

Journal of Biomolecular Structure and Dynamics

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The structural distortions of the duplex dodecamer d(ATTAACGTTAAT)2 monofunctionally alkylated by mitomycin C have been studied by the use of chemical probes reactivity and resonance Raman spectroscopy. This sequence contains the 5'-ACGT sequence for which mitomycin C was determined to present the best affinity (S. Kumar, R. Lipman, and M. Tomasz, Biochemistry 31, 1399 (1992)). Raman spectroscopy as well as osmium tetroxyde reactivity indicate that the distortion of the double helix structure is located around the central CG bases. Mitomycin C reacts exclusively with the 2-amino group of guanine and this binding does not disrupt the inter bases H-bonds, as indicated by chloroacetaldehyde reactivity. Although resonance Raman spectroscopy does not allow the handedness of the monoalkylated CG/GC sequence to be determined, it indicates a similarity between the base stacking and that which would be observed for alternating purine/pyrimidine sequences at high salt concentration.

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Recognition of mitomycin C-DNA monoadducts by UVRABC nuclease

Cited by 39 publications

References 0 publications

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

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

Mitomycinoid Alkaloids: Mechanism of Action, Biosynthesis, Total Syntheses, and Synthetic Approaches

Distortion After Monofunctional Alkylation by Mitomycin C of a Dodecamer Containing its Major Binding Site

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