PARP1 and PARylation facilitate transcription-coupled DNA repair by stabilizing the CSB–RNAPII complex
Bibliographic record
Abstract
Transcription-coupled nucleotide excision repair (TC-NER or TCR) is initiated when the ATPase Cockayne syndrome protein B (CSB) recognizes a DNA lesion stalled RNA polymerase II (RNAPII) and forms a stable complex. Here, we report that poly(ADP-ribose) polymerase-1 (PARP1), that plays a key role in the lesion recognition step of global genomic NER, also facilitates the earliest step of TCR. PARP1, which is associated with RNAPII during normal transcription, interacts with and stabilizes CSB on the lesion-stalled RNAPII. CSB stimulates PARP1's activity to form PAR, and in turn CSB is PARylated mainly at its N-terminal PAR-binding motif (PBM) to promote its stabilization with RNAPII, whereas its minor PARylation at the C-terminal domain suppresses its ATPase function, thus limiting the window of time for ATP-dependent lesion recognition by CSB. The loss of PARP1, treatment with inhibitors of PARP or poly(ADP-ribose) glycohydrolase (PARG) to prevent PAR synthesis or its catabolism to generate free PAR or engineering N-terminal PARylation-resistant CSB decrease the efficiency of cells for TCR. PARP1 mutant Caenorhabditis elegans larvae exhibit a pronounced TCR-deficient phenotype. Our findings uncover an evolutionarily conserved role of PARP1 and PAR metabolism in the initiation of TCR.
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 | 0.001 |
| 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".