Role of BRCA2/FANCD1 in Homologous Recombination
Julia Etchin, San Joe Filippo, Patrick Sung, Lumír Krejčí
Abstract
Julia Etchin, San Joe Filippo, Patrick Sung, Lumír Krejčí
Abstract
The molecular function of BRCA2 in homologous recombination has not been elucidated. We are using biochemical approaches as well as electron microscopy to validate the hypothesis that BRCA2 influences Rad51 recombinase activity by nucleating Rad51 onto ssDNA to promote the assembly of the Rad51 presynaptic filament, a pivotal intermediate in HR reactions. In addition, we have characterizaed the DNA binding properties of BRCA2-DBD fragment and examined variants of BRCA2 containing combinations of the Rad51-interaction and DNA binding motifs for the ability to target Rad51 to recombination substrates. By deciphering the functional significance of these interactions, we will be able to rationalize how mutations in BRCA2 lead to genome instability and breast cancer.
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The molecular function of BRCA2 in homologous recombination has not been elucidated. We are using biochemical approaches as well as electron microscopy to validate the hypothesis that BRCA2 influences Rad51 recombinase activity by nucleating Rad51 onto ssDNA to promote the assembly of the Rad51 presynaptic filament, a pivotal intermediate in HR reactions. In addition, we have characterizaed the DNA binding properties of BRCA2-DBD fragment and examined variants of BRCA2 containing combinations of the Rad51-interaction and DNA binding motifs for the ability to target Rad51 to recombination substrates. By deciphering the functional significance of these interactions, we will be able to rationalize how mutations in BRCA2 lead to genome instability and breast cancer.
Key concepts: RAD51, Homologous recombination, BRCA2 Protein, Recombinase, Genome instability, DNA, Genetics, Biology