Trp53-dependent DNA-repair is affected by the codon 72 polymorphism.
Oncogene
; 25(25): 3489-500, 2006 Jun 15.
Article
em En
| MEDLINE
| ID: mdl-16462765
ABSTRACT
Trp53 is arguably the most critical tumour suppressor gene product that inhibits malignant transformation. Besides mutations that inactivate Trp53 functions, genetic polymorphisms have been suggested to be risk factors for cancer. A polymorphic site at codon 72 in exon 4 encodes either an arginine amino acid (Trp53(72R)) or a proline residue (Trp53(72P)). Previous studies have shown that the Trp53(72R) form is more efficient in apoptosis induction, whereas the Trp53(72P) form was suggested to induce G1 arrest better. Here we report that Trp53(72P) is more efficient than Trp53(72R) in specifically activating several Trp53-dependent DNA-repair target genes in several cellular systems. Moreover, using isogenic cell lines and several DNA-repair assays, we show that Trp53(72P) cells have a significantly higher DNA-repair capacity than the Trp53(72R) cells. Furthermore, Trp53(72P)-expressing cells exhibit reduced micronuclei formation compared to Trp53(72R)-expressing cells, suggesting that genomic instability is reduced in these cells. Together, the data highlight the functional differences between the Trp53 polymorphic variants, and suggest that their expression status may influence cancer risk.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polimorfismo Genético
/
Transformação Celular Neoplásica
/
Proteína Supressora de Tumor p53
/
Reparo do DNA
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article