Inhibition of gene-specific repair of alkylation damage in cells depleted of poly(ADP-ribose) polymerase.
Nucleic Acids Res
; 22(22): 4620-4, 1994 Nov 11.
Article
em En
| MEDLINE
| ID: mdl-7984410
ABSTRACT
The role of the enzyme poly(adenosine diphosphate-ribose) polymerase (PADPRP) in DNA repair at the level of the gene was investigated with human HeLa cells in which PADPRP antisense transcripts are inducible with dexamethasone. After such induction, the cellular content of PADPRP is reduced by 90%. DNA damage and its repair was studied in the essential dihydrofolate reductase (DHFR) gene after exposure of the cells to either ultraviolet (UV) irradiation or the alkylating agent nitrogen mustard. The expression of the antisense construct had no effect on gene-specific repair of UV-induced pyrimidine dimers. In contrast, induced antisense cells were deficient in the gene-specific repair of nitrogen mustard-induced lesions. Dexamethasone itself did not inhibit gene-specific repair in control cells. Thus, PADPRP appears to participate in the gene-specific repair of alkylation damage, but not in the repair of UV-induced pyrimidine dimers. Clonal survival assays revealed that cells depleted of PADPRP showed an increased susceptibility to nitrogen mustard, supporting the notion that repair of essential genes is critical for cellular survival.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Dano ao DNA
/
Poli(ADP-Ribose) Polimerases
/
Reparo do DNA
Limite:
Humans
Idioma:
En
Revista:
Nucleic Acids Res
Ano de publicação:
1994
Tipo de documento:
Article