NSF Award
9419507
9419507 Jasin The repair of chromosomal DNA double-stranded breaks (DSBs) in mouse cells by homologous recombination will be studied. The hypothesis to be tested is that one pathway in the repair of DSBs in mammalian cells is homologous recombination, and that DSBs will stimulate gene targeting and interchromosomal recombination. The approach involves the introduction of chromosomal DSBs in cultured cells through the expression of rare-cutting, site-specific endonucleases. The first objective of the proposal investigates the repair of DSBs in mouse embryonic stem (ES) cells. In particular, it will be determined if chromosomal DSBs will stimulate gene targeting. The second objective investigates whether DSBs will stimulate interchromosomal recombination. %%% The repair of DNA double stranded breaks is crucial for the maintenance of genomic integrity in all organisms. Altered repair processes and the inability to repair double stranded breaks will result in mutagenesis and oncogenic transformation, and ultimately cell death. Both homologous and non-homologous processes are expected to be involved in the repair of such breaks in mammalian cells. The understanding that is gained about normal cellular repair process and homologous recombination will have a broad and long-range impact on health, medicine, and basic science. ***
