BMI1 Interacts with FANCD2 at DNA Lesions and Prevents Chromosome Breaks
Bibliographic record
Abstract
Abstract Bmi1 is a major determinant of hematopoietic stem cell (HSC) self-renewal. To date, much of our understanding of Bmi1 function comes from studies linking it to p16ink4a-Rb and p19arf-p53 pathways. However, several observations have raised the possibility that Bmi1 requirement for the maintenance of stem cell self-renewal ability extends far beyond its role in repressing the INK4a/ARF locus. The phenotypical similarities shared between Bmi1 deficiency in mouse and Fanconi Anemia (FA) patients (e.g., congenital aplastic anemia) together with the reported mono-ubiquitin ligase activities of proteins in both complexes and the emerging concept connecting DNA repair to stem cell properties, prompted us to evaluate Bmi1 implication in DNA damage repair. We now report that, like FA cells, Bmi1-deficient HSCs accumulate at G2/M phase of cell cycle. Moreover, Bmi1 is rapidly recruited to DNA damage foci in a PI3 kinase like kinase (PIKK)-dependant manner, in several cell types including hematopoietic stem cells. Upon induction of DNA lesions, Bmi1 interacts with several proteins involved in DNA damage response including γ-H2AX, MDC1, RAP80 and the monoubiquitinated form of FANCD2. We found that Bmi1 depletion did not hinder DNA damage-induced γ-H2AX foci formation and that RNF8-dependent signaling cascade is functional in absence of Bmi1. Furthermore, as observed in FA, loss of Bmi1 is associated with occurrence of spontaneous chromosome breaks and increased sensitivity to clastogenic agents. These chromosome breaks occur although FANCD2 monoubiquitination and loading onto chromatin is preserved. Together this work reveals an unsuspected role for Bmi1 in securing chromosome integrity and connects Polycomb genes to FA repair pathway.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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".