DNA interstrand

Lee, C.-S. Gibson, N. W. DNA interstrand cross-links induced by the cyclopropylpyrro-loindole antitumor agent bizelesin are reversible upon exposure to alkali. Biochemistry 1993, 32, 9108-9144. 

Qu, Y. Scarsdale, N. J. Tran, M. C. Farrell, N. Cooperative effects in long-range 1,4 DNA-DNA interstrand crosslinks formed by polynuclear platinum complexes an unexpected syn-orientation of adenine bases outside the binding sites. J Biol Inorg Chem 2003, 8, 19-28. 

Kasparkova, J. Zehnulova, J. Farrell, N. Brabec, V. DNA interstrand crosslinks of novel antitumor trinuclear platinum complex BBR. Conformation, recognition by HMG-domain proteins and nucleotide excision repair. J Biol Chem 2002, 277, 48076-48086. 

Ewig, R.A.C., and Kohn, K.W. (1977) DNA - protein cross-linking and DNA interstrand cross-linking by haloethylnitrosoureas in L1210 cells. Cancer Res. 38, 3197. 

Niedernhofer LJ, Odijk H, Budzowska M et al. The stmeture-speeifie endonuelease Erccl-Xpf is required to resolve DNA interstrand cross-link-induced double-strand breaks. Mol Cell Biol 2004 24 5776-5787. 

Prasher JM, Lalai AS, Heijmans-Antonissen C et al. Redueed hematopoietie reserves in DNA interstrand erosslink repair-defleient Ereel-/- miee. Emfeo J2005 24 861-871. 

Hong IS, Greenberg MM (2005) Efficient DNA interstrand cross-link formation from a nucleotide rad ical. J Am Chem Soc 127 3692-3693... 

Wojcik A, Bochenek A, Lankoff A, Risowska A, Padjas A, von Sonntag C, Obe G (2005) DNA interstrand crosslinks are induced in cells prelabelled with 5-bromo-2 -deoxyuridine and exposed to UVC radiation, in preparation... 

Bridgewater LC, Manning FCR, Patierno SR. 1994a. Base-specific arrest of in vitro DNA replication by carcinogenic chromium relationship to DNA interstrand crosslinking. Carcinogenesis 15(11) 2421-2427. 

DNA interstrand cross-links were also purified and found to be formed between two deoxyguanosines, but this requires a major contortion of the DNA structure and may only occur when an alternate purine is not in close proximity on the same strand [12]. This presumably explains why interstrand cross-links occur at less than 1% of the total platination of DNA. One other adduct that was shown to form in vitro was a cross-link between deoxyguanosine and glutathione [18]. This adduct could be produced when... 

Despite knowing the structures of all of the DNA lesions, it remains to be determined if any one lesion is more or less toxic to the cells. As discussed above, it was originally thought that DNA interstrand cross-links were the critical lesion. Once it was realized that these lesions are very rare, opinions shifted to suggest that DNA intrastrand cross-links are more cytotoxic. Unfortunately, there is no specific data that implicates either type of lesion in cytotoxicity. For some drugs like nitrosoureas, DNA repair pathways that remove only selected lesions (i.e., 0(6)-methylguanine DNA methyltransferase) have helped to define the role of a particular lesion [24], No separate pathway has been found for repair of a specific cisplatin adduct, so this approach has not been informative. A number of experiments have been performed in which specific adducts on defined DNA sequence, have been transfected into cells. This approach has shown that an adduct inhibits replication or transcription, but this does not directly address the question of mechanism of cytotoxicity. 

Another alkylating drug in clinical use is mitomycin C. As a natural product isolated from Stremtomyces lavendulae, mytomycin C is an aziridine compound, which is closely related to nitrogen mustards. This compound is best known to the DNA repair field as a DNA interstrand crosslinking agent. Mytomycin C has been used to treat breast cancer and cancers of the gastrointestinal tract. 

Narayanaswamy, M. et al. An assay combining high-performance liquid chromatography and mass spectrometry to measure DNA interstrand cross-linking efficiency in oligonucleotides of varying sequences. Ana/. Biochem. 2008, 374,173-181. 

Dronkert ML, Kanaar R. Repair of DNA interstrand cross-links. Mutat. Res. 2001 486 217-247. 

Mu D, Bessho T, Nechev LV, Chen DJ, Harris TM, Hearst JE, Sancar A. DNA interstrand cross-hnks induce futile repair synthesis in mammalian cell extracts. Mol. Cell. Biol. 2000 20(7) 2446-2454. 

Edfeldt NB, Harwood EA, Sigurdsson ST, Hopkins PB, Reid BR. Solution structure of a nitrous acid-induced DNA interstrand DNA cross-link. Nucleic Acids Res. 2204 32 2785-2794. 

Busulfan is a bifunctional alkylating agent. It consists of two methanesulfonate groups attached at opposite ends of a four-carbon alkyl chain. Alkylating agents form covalent DNA interstrand cross-links that inhibit DNA synthesis. Toxicity of busulfan s alkylation of intercellular nucleophiles is associated with its... 

Measurement of Drug-Induced DNA Interstrand Crosslinking Using the Single-Cell Gel Electrophoresis (Comet) Assay... 

Figure 2 illustrates DNA interstrand crosslinking in human lymphocytes. In... 

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