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Publication Detail

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

Authors: Weng, Mao-wen; Zheng, Yi; Jasti, Vijay P; Champeil, Elise; Tomasz, Maria; Wang, Yinsheng; Basu, Ashis K; Tang, Moon-shong

Published In Nucleic Acids Res, (2010 Nov)

Abstract: 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.

PubMed ID: 20647419 Exiting the NIEHS site

MeSH Terms: DNA Adducts/chemistry; DNA Adducts/metabolism*; DNA Breaks, Double-Stranded; DNA Repair*; Endodeoxyribonucleases/metabolism*; Escherichia coli Proteins/metabolism*; Mitomycin/chemistry; Mitomycin/metabolism*; Models, Genetic*

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