Abstract A07: The RAD51 paralog complex SWS1-SWSAP1 is critical for homologous recombination in the mouse

Homologous recombination (HR), also termed homology-directed repair, is a major pathway for the repair of DNA double-strand breaks (DSBs) generated by DNA damaging agents, replication fork collapse and during meiosis. Failure to repair DSBs correctly causes genomic instability, leading to mutagenesis, and developmental defects. Moreover, defects in HR impact the response to many therapeutics. Components of the HR machinery include BRCA2 and five RAD51 paralogs, which are critical for RAD51 assembly onto single-stranded DNA, an important intermediate for homologous strand invasion. Disruption of these HR genes in mice results in embryonic lethality (pre-implantation to mid-gestation defects), developmental defects (e.g., sterility), and tumorigenesis. Recently, the Shu complex, composed of SWS1 and SWSAP1 subunits, was identified in human cells as a potential RAD51 paralog complex, since it functions with RAD51 to promote mitotic HR like its ortholog in yeast. Here, we show that the mouse Shu complex interacts with the ubiquitously expressed RAD51 recombinase and also with the meiosis-specific DMC1 recombinase. Knockout mice lacking one or both Shu complex subunits are viable and show no obvious developmental defects, except in gonads of both female and male mice, which are infertile. Analyses in males demonstrate that Shu complex is required for proper homologous synapsis and for the formation of RAD51 and DMC1 foci very early in meiotic prophase I. Our preliminary results in...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Homologous Recombination Defects: Poster Presentations - Proffered Abstracts Source Type: research