<scp>BRCA1</scp> transports the <scp>DNA</scp> damage signal for <scp>CDDP</scp>‐induced centrosome amplification through the centrosomal Aurora A
Bibliographic record
Abstract
Breast cancer gene 1 (BRCA1) plays roles in DNA repair and centrosome regulation and is involved in DNA damage-induced centrosome amplification (DDICA). Here, the centrosomal localization of BRCA1 and the kinases involved in centrosome duplication were analyzed in each cell cycle phase after treatment with DNA crosslinker cisplatin (CDDP). CDDP treatment increased the centrosomal localization of BRCA1 in early S-G2 phase. BRCA1 contributed to the increased centrosomal localization of Aurora A in S phase and that of phosphorylated Polo-like kinase 1 (PLK1) in late S phase after CDDP treatment, resulting in centriole disengagement and overduplication. The increased centrosomal localization of BRCA1 and Aurora A induced by CDDP treatment involved the nuclear export of BRCA1 and BRCA1 phosphorylation by ataxia telangiectasia mutated (ATM). Patient-derived variants and mutations at phosphorylated residues of BRCA1 suppressed the interaction between BRCA1 and Aurora A, as well as the CDDP-induced increase in the centrosomal localization of BRCA1 and Aurora A. These results suggest that CDDP induces the phosphorylation of BRCA1 by ATM in the nucleus and its transport to the cytoplasm, thereby promoting the centrosomal localization Aurora A, which phosphorylates PLK1. The function of BRCA1 in the translocation of the DNA damage signal from the nucleus to the centrosome to induce centrosome amplification after CDDP treatment might support its role as a tumor suppressor.
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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".