Thymine Crosslinks

Dizdaroglu M, Simic MG (1984a) Radiation-induced formation of thymine-thymine crosslinks. Int J Radiat Biol 46 241-246... 

Psoralens can react by two different routes upon photoactivation (Parsons, 1980 Pathak, 1984). The first route is through the well-known photoreaction mechanism that principally involves intercalation within double-stranded DNA or RNA with the formation of adducts with adjacent thymine bases. The furan-side and pyrone-side rings in psoralen both can form cycloaddition products with the 5,6-double bond of thymine to create a crosslink between two DNA strands (Reaction 57) or to a lesser extent, within double-strand regions of RNA. 

Oxygen-free reactions of psoralens, when in close proximity to the target, proceed via the first excited states in which the 3,4-and the 4, 5 7r-bonds of the pyrone and furan moieties, respectively, can undergo C4-cyclization reactions with, e.g., unsaturated bonds of lipids, or the C5=C6 double bonds of thymine in DNA. In reactions with DNA the psoralen is believed to intercalate with DNA in the dark. Subsequent irradiation at 400 nm usually leads to furan-side 4, 5 -monoadduct formation, whereas irradiation at 350 nm increases the formation of crosslinks in which the furan and pyrone rings form C4 cycloadducts to thymines on opposite strands [95], Subsequent irradiation of the 4, 5 -monoadducts at 350 nm leads to formation of crosslinks and conversion into pyrone-side 3,4-monoadducts. Shorter wave-... 

What is the difference between the structure of the thymine dimer in DNA irradiated in vivo and in dry films What would you expect to be the structure of thymine dimers in crosslinked VBT photoresist ... 

The induced damage may take the form of single-strand breaks, induction of thymine dimers, or DNA-protein crosslinks... 

Pearlman et al. (196) built a model of a psoralen-DNA covalently crosslinked complex based on the crystal structure of a thymidine-psoralen-thymine complex, using computer graphics and molecular mechanics calcu-... 

Xerri, B., Morell, C., Grand, A., Cadet, J., Cimino, P., and Barone, V. (2006) Radiation-induced formation of DNA intrastrand crosslinks between thymine and adenine bases. A theoretical approach. Org. Biomol. Chem., 4, 3986-3992. 

Photocyclodimerization is now considered to be a major factor in mutagenesis in DNA and polynucleotides. The reaction involves the photoinduced dimerization of pyrimidine bases such as thymine. The crosslinking which results causes a defect in the coding sequence and can cause other cell damage. 

The ability of Polt/ and Polt to bypass a variety of structurally diverse and potentially mutagenic lesions in vitro has been analyzed extensively. These biochemical studies revealed that the efficiency and pattern of nucleotide incorporation opposite DNA damaged sites is distinct for the two RadSO paralogp. In some cases, Polt/ readily bypasses a lesion, whereas Polt does it inefficiently, or not at all. An example of Poltj s and Polt s disparate TLS activities is observed at thymine CPDs and cisplatin-induced dG intrastrand crosslinks. Polt/ efficiently facilitates robust bypass of both CPDs (Johnson et aL, 2000c Masutani et aL, 2000 McGuUoch et aL, 2004) and platinum-GG cross links (Vaisman et aL, 2000) in vitro, whereas Polt bypasses the GPD in a limited manner (Tissier et aL, 2000a) that is sequence context dependent (Vaisman et al., 2003) and is incapable of nucleotide incorporation opposite a cisplatin adduct (McDonald et al., 2001). 

Other functional groups that can be used to form photocrosslinkable polymers are alkyne, male-imides, stilbene, styrene, 1,2,3-thiadiazole, thymine, and anthracene. Pendant groups with anthracene moiety, however, are believed to crosslink by a 47t + An type of cycloaddition ... 

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