Damage distribution and mutation spectrum: the case of 8-methoxypsoralen plus UVA in mammalian cells.
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.
Sage
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E
CNRS URA 1292, Institut Curie, Paris, France.
Bredberg
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A
D000818:Animals; D001482:Base Composition; D001483:Base Sequence; D002460:Cell Line; D002869:Chromosome Aberrations; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology; D004926:Escherichia coli / Q000235:genetics; D005822:Genetic Vectors; D008730:Methoxsalen / Q000633:toxicity*; D008969:Molecular Sequence Data; D009154:Mutation; D010957:Plasmids; D012343:RNA, Transfer / Q000235:genetics*; D014466:Ultraviolet Rays; D014709:Vero Cells
D012343:RNA, Transfer; D008730:Methoxsalen