CSB interacts with BRCA1 in late S/G2 to promote MRN- and CtIP-mediated DNA end resection
Bibliographic record
Abstract
CSB, a member of the SWI2/SNF2 superfamily, has been implicated in evicting histones to promote the DSB pathway choice towards homologous recombination (HR) repair. However, how CSB promotes HR repair remains poorly characterized. Here we demonstrate that CSB interacts with both MRE11/RAD50/NBS1 (MRN) and BRCA1 in a cell cycle regulated manner, with the former requiring its WHD and occurring predominantly in early S phase. CSB interacts with the BRCT domain of BRCA1 and this interaction is regulated by CDK-dependent phosphorylation of CSB on S1276. The CSB-BRCA1 interaction, which peaks in late S/G2 phase, is responsible for mediating the interaction of CSB with the BRCA1-C complex consisting of BRCA1, MRN and CtIP. While dispensable for histone eviction at DSBs, CSB phosphorylation on S1276 is necessary to promote efficient MRN- and CtIP-mediated DNA end resection, thereby restricting NHEJ and enforcing the DSB repair pathway choice to HR. CSB phosphorylation on S1276 is also necessary to support cell survival in response to DNA damage-inducing agents. These results altogether suggest that CSB interacts with BRCA1 to promote DNA end resection for HR repair and that although prerequisite, CSB-mediated histone eviction alone is insufficient to promote the pathway choice towards HR.
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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) | 0.003 | 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".