Synthetic lethal genetic interactions between Rad54 and PARP-1 in mouse development and oncogenesis.

ABSTRACT: Mutations in DNA repair pathways are frequent in human cancers. Hence, gaining insights into the interaction of DNA repair genes is key to development of novel tumor-specific treatment strategies. In this study, we tested the functional relationship in development and oncogenesis between the homologous recombination (HR) factor Rad54 and Parp-1, a nuclear enzyme that plays a multifunctional role in DNA damage signaling and repair. We introduced single or combined Rad54 and Parp-1 inactivating germline mutations in Ptc1 heterozygous mice, a well-characterized model of medulloblastoma, the most common malignant pediatric brain tumor. Our study reveals that combined inactivation of Rad54 and Parp-1 causes a marked growth delay culminating in pe

SUBMITTER: Tanori M 

PROVIDER: S-EPMC5731848 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature