Abstract 2988: A PP6-phosphatase complex is required for homology-directed repair of DNA double-strand breaks
Bibliographic record
Abstract
Abstract DNA double-strand breaks (DSBs) are among the most lethal lesions associated with genome stability which, when destabilized, predisposes organs to cancers. DSBs are primarily fixed either with little fidelity by non-homologous end joining (NHEJ) repair or with high fidelity by homology-directed repair (HDR). The phosphorylated form of H2AX on serine 139 (g-H2AX) is a marker of DSBs. It is dephosphorylated by PP2A-like protein phosphatases (PP2A, PP4, and PP6). Here, we identify three novel PP6 subunits. Several PP6c (the catalytic subunit of PP6)-containing heterotrimeric complexes show phosphatase activities against g-H2AX in the in vitro phosphatase assays using bacterially-produced proteins, providing direct evidence that the PP6 holoenzyme is a PP6c-containing heterotrimeric complex. Furthermore, depletion of PP6c, PP6R2, or MyPT1 leads to defective HDR, and expression of phosphatase-inactive PP6c fails to rescue this defect. Chromatin immunoprecipitation assays demonstrated that PP6c is recruited to the region adjacent to the DSB sites. Expression of PP6R2, but not PP6c or MyPT1, is associated with improved overall survival in patients with breast cancer at five years (n=100, p=0.038). Taken together, our results suggest that the PP6-PP6R2-MyPT1 complex is required for HDR and PP6R2 is a potential therapeutic target. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2988.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".