Strand bias of ultraviolet light-induced mutations in a transcriptionally active gene in human cells.
Mol Carcinog
; 14(3): 214-25, 1995 Nov.
Article
em En
| MEDLINE
| ID: mdl-7576114
ABSTRACT
Ultraviolet (UV)-induced repair and mutational spectra were analyzed in an inducible marker gene, the metallothionein-l/guamine-xanthine phosphoribosyl transferase (gpt) fusion gene, carried by an Epstein-Barr virus-derived shuttle vector episomically maintained in human cells. The repair rate of UV photodimers from the shuttle-vector molecules was typical of transcriptionally active sequences, 70% of the dimers being removed within 8 h after irradiation. The spectrum obtained under basal gene transcription was compared with that obtained under induced transcription. In both cases, base substitutions at dipyrimidine sequences predominated. Multiple mutations and deletions probably due to recombinational events induced by UV damage were also observed. Most of the UV-mutated dipyrimidine sites were located in the transcribed strand and were independent of the transcriptional activity of the target gene. In contrast, the distribution of mutations throughout the coding region of the gpt gene was affected by transcription, with a preferential clustering of mutations occurring in the 3' half of the gene after transcription induction. The strand bias observed in the UV spectra most likely reflects selection for nonfunctional gpt protein.
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Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
/
Raios Ultravioleta
/
DNA
/
Mutação
Limite:
Humans
Idioma:
En
Ano de publicação:
1995
Tipo de documento:
Article