RESUMEN

An oligodeoxyribonucleotide (ODN) containing three C5-substituted arabinofuranosyluracils was synthesized by the post-synthetic modification method from the ODN containing three C5-substituted 2,2'-anhydrouridines. The stability of the modified ODN/DNA duplex was lower than that of the corresponding normal duplex but that of the modified ODN/RNA duplex showed little change. The modified ODN could induce RNase H activity and was resistant against nuclease.

Asunto(s)

Arabinofuranosil Uracilo/síntesis química , Arabinofuranosil Uracilo/genética , Oligodesoxirribonucleótidos Antisentido/síntesis química , Oligodesoxirribonucleótidos Antisentido/genética

RESUMEN

Germline mutations in BRCA1 confer a high risk of breast and ovarian tumors. The role of BRCA1 in tumor suppression is not yet understood, but both transcription and repair functions have been ascribed. Evidence that BRCA1 is involved in DNA repair stems from its association with RAD51, a homolog of the yeast protein involved in the repair of DNA double-strand breaks (DSBs) by homologous recombination. We report here that Brca1-deficient mouse embryonic stem cells have impaired repair of chromosomal DSBs by homologous recombination. The relative frequencies of homologous and nonhomologous DNA integration and DSB repair were also altered. The results demonstrate a caretaker role for BRCA1 in preserving genomic integrity by promoting homologous recombination and limiting mutagenic nonhomologous repair processes.

Asunto(s)

Proteína BRCA1/genética , Reparación del ADN/genética , Animales , Arabinofuranosil Uracilo/análogos & derivados , Arabinofuranosil Uracilo/genética , Línea Celular , Cromosomas/genética , Daño del ADN/genética , Proteínas de Unión al ADN/genética , Marcación de Gen , Ratones , Ratones Noqueados , Mutación , Proteínas Proto-Oncogénicas/genética , Recombinasa Rad51 , Recombinación Genética , Proteína de Retinoblastoma/genética , Células Madre/metabolismo , Timidina Quinasa/genética , Transfección