Repair of DNA-double-strand breaks induced by the chemotherapeutic drug Topotecan in mamma carcinoma cells with genetic defects in the BRCA1 or BRCA2 genes

Abstract

The tumour suppressor genes BRCA1 and BRCA2 play an essential role for homologous recombination during embryonic development and for maintenance of genomic stability during the adult life. The central question of this doctoral thesis is: Do cells with defects in both alleles of either BRCA1 or BRCA2, such as tumour cells of inheritable breast cancer, have deficiency in repairing DNA-double-strand breaks induced by the chemotherapeutic drug Topotecan when compared with BRCA1- and BRCA2-proficient cells?

Die Tumor-Suppressor-Gene BRCA1 und BRCA2 spielen eine essentielle Rolle in der homologen Rekombination während der Embryonalentwicklung sowie im weiteren Leben durch Sicherung der genomischen Stabilität. Die zentrale Frage lautet: Können Zellen mit Defekten in beiden Allelen des BRCA1- oder BRCA2-Gens, wie z.B. Tumorzellen im erblich bedingten Brustkrebs, Topotecan-erzeugte DNA-Doppelstrangbrüche schlechter reparieren als Zellen ohne diese Defekte?