High rate of CAD gene amplification in human cells deficient in MLH1 or MSH6

AUTOR(ES)

Chen, Sihong

FONTE

The National Academy of Sciences

RESUMO

MutS and MutL homologs have been implicated in multiple genetic stabilization pathways. The activities participate in the correction of DNA biosynthetic errors, are involved in cellular responses to certain types of DNA damage, and serve to ensure the fidelity of genetic recombination. We show here that the rate of CAD (carbamyl-P synthetase/aspartate transcarbamylase/dihydroorotase) gene amplification is elevated 50- to 100-fold in human cell lines deficient in MLH1 or MSH6, as compared with mismatch repair-proficient control cells. Fluorescence in situ hybridization indicates that these amplification events are the probable consequence of unequal sister chromatid exchanges involving chromosome 2, as well as translocation events involving other chromosomes. These results implicate MutSα and MutLα in the suppression of gene amplification and suggest that defects in this genetic stabilization function may contribute to the cancer predisposition associated with mismatch repair deficiency.

Documentos Relacionados

• Immunoexpression of TS, p53, COX2, EGFR, MSH6 and MLH1 biomarkers and its correlation with degree of differentiation, tumor staging and prognostic factors in colorectal adenocarcinoma: a retrospective longitudinal study
• Mutation screening of MSH2 and MLH1 mRNA in hereditary non-polyposis colon cancer syndrome.
• Mutator Phenotypes Conferred by MLH1 Overexpression and by Heterozygosity for mlh1 Mutations
• Decreased Expression of the DNA Mismatch Repair Gene Mlh1 under Hypoxic Stress in Mammalian Cells
• Direct association of Bloom’s syndrome gene product with the human mismatch repair protein MLH1