Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We determined the distribution of monoadducts and biadducts induced in the supF tRNA gene carried by the shuttle vector pZ189, after exposure to 8-methoxypsoralen (8-MOP) plus a double UVA (365 nm) irradiation. These data were compared to our previously published 8-MOP-photoinduced mutation spectrum obtained after propagation of the damaged shuttle vector in mammalian cells. One mutational hot spot in an ATAT/TATA sequence is targeted at a hot spot of biaddition. A second hot spot is not related to the presence of photoadducts either at or near the site. Moreover, it is located in a sequence which can be defined as 'mutation-prone'. Mutations occurring at GC base pairs are not targeted at sites of photoaddition, and may result from a decrease in fidelity of DNA polymerase when copying the damaged vector.
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PMID:Damage distribution and mutation spectrum: the case of 8-methoxypsoralen plus UVA in mammalian cells. 186 86

The photoreaction of 8-methoxypsoralen (8-MOP) with DNA fragments of defined sequence was studied. We took advantage of the blockage by bulky adducts of the 3'-5'-exonuclease activity associated with the T4 DNA polymerase. The action of the exonuclease is stopped by biadducts as well as by monoadducts. The termination products were analyzed on sequencing gels. A strong sequence specificity was observed in the DNA photobinding of 8-MOP. The exonuclease terminates its digestion near thymine residues, mainly at potentially cross-linkable sites. There is an increasing reactivity of thymine residues in the order T less than TT much less than TTT in a GC environment. For thymine residues in cross-linkable sites, the reactivity follows the order AT much less than TA approximately TAT much less than ATA less than ATAT less than ATATAA. Repeated A-T sequences are hot spots for the photochemical reaction of 8-MOP with DNA. Both monoadducts and interstrand cross-links are formed preferentially in 5'-TpA sites. Our results highlight the role of the sequence and consequently of the conformation around a potential site in the photobinding of 8-MOP to DNA.
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PMID:Sequence context effects on 8-methoxypsoralen photobinding to defined DNA fragments. 365 86