Interstrand DNA cross-linking

Fanconi anemia arises from a decreased abiiity to repair interstrand DNA cross-links. 

Cisplatin Forms intrastrand and interstrand DNA cross-links binding to nuclear and cytoplasmic proteins Non-small cell and small cell lung cancer, breast cancer, bladder cancer, gastroesophageal cancer, head and neck cancer, ovarian cancer, germ cell cancer Nausea and vomiting Nephrotoxicity, peripheral sensory neuropathy, ototoxicity, nerve dysfunction... 

In the absence of 02, there is little if any strand breakage instead the drug binds covalently to DNA (Povirk and Goldberg 1982, 1984) and induces, under certain conditions, interstrand DNA cross-links (Xu et al. 1997) with the same base specificity as SSB formation in the presence of 02 (Povirk and Goldberg 1985a). 

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. 

Nitrogen mustard derivative forms interstrand DNA cross-links selective cytotoxicity for lymphocytes... 

Harris, T.M., and Rizzo, C.J. (2008) Interstrand DNA cross-links induced by ra,[3-unsaturated aldehydes derived from lipid peroxidation and environmental sources. Acc. Chem. Res., 41, 793-804. 

Interstrand DNA Cross-Linking l,N2-Deoxyguanosine Adducts Derived from oc,p-Unsaturated Aldehydes ... 

Some B-family DNA polymerases can also be involved in translesion synthesis, such as Pol II iri coli and Pol C, which is present in most eukaryotes [7-9]. B-family translesion synthesis DNA polymerases are involved in a DNA repair pathway of some interstrand DNA cross-links [39-42] and in translesion synthesis of some adduct/lesions (see below). 

UV radiation and some chemical agents damage DNA by creating intrastrand or interstrand DNA cross-links (Figure 17.3). Intrastrand cross-links, which occur when covalent bonds form between two bases on the same strand of DNA, tend to distort the double helix. Interstrand cross-links, which occur when covalent bonds form between two bases on opposite strands of the double helix, are particularly problematic since they prevent the melting at the point of the cross-link and pose absolute blocks to replication and transcription. 

Psoralen is among the agents that forms interstrand DNA cross-links. It is a photosensitizing agent found in plants and has been used in a therapeutic regimen along with UV-A to treat psoriasis and other skin disorders. Psoralen can intercalate into DNA, absorb UV-A, and subsequently react with DNA, principally at... 

Intrastrand and interstrand DNA cross-links are also formed in DNA by another important class of chemotherapeutic drugs-the cisplatins. The majority of the adducts formed in vivo and in vitro are 1,2-intrastrand d(GpG) and d(ApG) crosslinks that represent 80-90% of the bound platinum. In addition 1,3-intrastrand d(GpTpG) cross-links and a small percentage of interstrand cross-links and monofunctional adducts are formed [127]. 

Carboplatin is a platinum coordination complex that produces predominantly interstrand DNA cross-links causing... 

Sulfur mustard has been found to be genotoxic and mutagenic in several microbial assays. The agent caused alkylation of DNA in the yeast Saccharo-myces cerevisiae (Kircher and Brendel 1983) and interstrand DNA cross-links (Venitt 1968) and inhibition of DNA synthesis (Lawley and Brookes 1965) in Escherichia coli. Using the histidine reversion assay, Stewart et al. (1989a) found that sulfur mustard induced point mutations in Salmonella typhimurium strain TA102 and frameshift mutations in TA 97 but neither type of mutation in strains TA98 and TAIOO. 

P. Lin, E. L. Vaughan and I. A. Bernstein, Formation of Interstrand DNA Cross-Links by Bis-(2-chloroethyl)Sulfide (BCES) A Possible Cytotoxic Mechanism in Rat Keratinocytes, Biochem. Biophys. Res. Commun., 1996, 218, 556-561. 

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