Suppression of high-fidelity double-strand break repair in mammalian chromosomes by pifithrin-alpha, a chemical inhibitor of p53.
DNA Repair (Amst)
; 2(1): 1-11, 2003 Jan 02.
Article
em En
| MEDLINE
| ID: mdl-12509264
ABSTRACT
We investigated the effect of pifithrin-alpha (PFTalpha), a chemical inhibitor of p53, on DNA double-strand break (DSB) repair in mammalian chromosomes. Thymidine kinase-deficient mouse fibroblasts were stably transfected with DNA substrates containing one or two recognition sites for yeast endonuclease I-SceI embedded within a herpes simplex virus thymidine kinase gene. Genomic DSBs were induced by introducing an I-SceI expression plasmid into cells in the presence or absence of 20 microM PFTalpha. From cells containing the DNA substrate with a single I-SceI site we recovered low-fidelity nonhomologous end-joining (NHEJ) events in which one or more nucleotides were deleted or inserted at the DSB. From cells containing the substrate with two I-SceI sites we recovered high-fidelity DNA end-joining (precise ligation (PL)) events. We found that treatment of cells with PFTalpha caused a 5-10-fold decrease in recovery of PL but decreased recovery of NHEJ by less than two-fold. Deletion sizes associated with NHEJ were unaffected by treatment with PFTalpha. Our work suggests the possibility that p53 facilitates high-fidelity DSB repair while playing little or no role in mutagenic NHEJ.
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Base de dados:
MEDLINE
Assunto principal:
Tiazóis
/
Tolueno
/
Proteína Supressora de Tumor p53
/
Reparo do DNA
Limite:
Animals
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article