DNA, interstrand cross links

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. 

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. 

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

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. 

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. 

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... 

Pu Y, Lin P, Vaughan FL et al. (1995). Appearance of interleukin la relates DNA interstrand cross-links and cytotoxicity in cultured human keratinocytes exposed to bis-(2-chloroethyl)sulphide. J Appl Toxicol, 15, 477 -82. 

Zou, Y., Van Houten, B., and Farrell, N. (1994) Sequence specificity of DNA-DNA interstrand cross-link formation by cisplatin and dinuclear platinum complexes. Biochemistry, 33, 5404-5410. 

Scheme 9.3 DNA interstrand cross-link formation mediated by the acrolein-derived y-OH-PdC adduct.

Lehoczky, P., McHugh, P.J., and Chovanex, M. (2007) DNA interstrand cross-link repair in Saccharomyces cerevisiae. FEMS Microbiol. Rev., 31, 109-133. 

Zwelling LA, Anderson T, Kohn KW. DNA-protein and DNA interstrand cross-linking by cis- and trans platinum [II] Diamminedichloride in LI2IO mouse leukemia cells and relation to cytotoxicity. Cancer Res 1979 39 365-369. 

The mechanism of the cytotoxic action of the cis - diammine -dichloroplatinum (II) complex (cis - DPP) is still unknown but there is much evidence indicating that DNA is the main target in a variety of biological systems ( 1 ). Three hypotheses are being considered that imply a bifunctional coordination of the cis -Pt (NH3)2 moiety to DNA interstrand cross-linking (, ),... 

Tra/75-[(NH3)2PtCl2] (see Figure 9) forms predominantly interstrand cross-links that are 1,3- and, to a lesser extent, 1,4-adducts. Adducts form at XNG and XNNG sequences (where X = A or C and N is any intervening nucleotide) via purine N-7 and cytosine N-3 atoms. DNA interstrand cross-linking by the platinum reagents occurs predominantly between two N-7 atoms of G residues on opposite strands. The 5 GC3 sequence within a miniduplex is better able than the 5 GC3 sequence to form a bridge with c/s-[(NH3)2Pt +], because the former has the more appropriate spatial orientation of donor... 

Huang, H., Hopkins, P. B. (1993). DNA interstrand cross-linked by formaldehyde Nucleotide sequence preference and covalent structure of the predominant cross-link formed in synthetic oligonucleotides, J. Am. Chem. Soc., 115 9402. 

Ponti M, Souhami RL, Fox BW, et al. DNA interstrand cross-linking and sequence selectivity of dimethanesulfonates. Br J Cancer 1991 63 743-747. 

The structure of the adducts of platinum derivatives with DNA continues to be of interest because of their use and potential as anticancer drugs. The specificity of DNA interstrand cross-links formed between the ineffective rranj-diamminechloroplatinum(II) has been determined as being preferentially between complementary guanine and cytosine residues. In addition, the rate of cross-linking with the trans isomer was found to be lower than that for the clinically active cis compound. The NMR solution structure of a DNA duplex containing the cis-platinumdiammine N7(G), N7(G) adduct has been determined. A second NMR structure examines adduct formation in an intrastrand cross-link created in a self-complementary duplex. A pair of enantiomeric Pt(II) complexes has been synthesised and their cytotoxicity has been evaluated. [Pt(RR-eaP)Cl2] (eap= N,N-diethyl-2,4-pentadiamine) was found to be more active in leukaemia cells but the difference was not as great as expected. ... 

Bessho, T., Mu, D., and Sancar, A. (1997). Initiation of DNA interstrand cross-link repair in humans The nucleotide excision repair system makes dual incisions 5 to the cross-linked base and removes a 22- to 28-nucleotide long damage free strand. 

Hong IS, Ding H, Greenberg MM. Oxygen independent DNA interstrand cross-link formation by a nucleotide radical. / Am Chem Soc. 2006 128 485-491. 

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