Abstract A07: The RAD51 paralog complex SWS1-SWSAP1 is critical for homologous recombination in the mouse
Bibliographic record
Abstract
Abstract 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 indicate that the mouse Shu complex is also important for mitotic HR. Therefore, we propose that Shu complex ensures the assembly of RAD51 and DMC1 proteins into nucleoprotein filaments on resected DSBs to promote successful homology search and strand invasion, for completion of meiotic and mitotic recombination. Citation Format: Rohit Prakash, Carla Manuela Abreu, Scott Keeney, Maria Jasin. The RAD51 paralog complex SWS1-SWSAP1 is critical for homologous recombination in the mouse [abstract]. In: Proceedings of the AACR Special Conference on DNA Repair: Tumor Development and Therapeutic Response; 2016 Nov 2-5; Montreal, QC, Canada. Philadelphia (PA): AACR; Mol Cancer Res 2017;15(4_Suppl):Abstract nr A07.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.009 | 0.005 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".