Detection of an Involvement of the Human Mismatch Repair Genes <b> <i>hMLH1</i> </b> and <b> <i>hMSH2</i> </b> in Nucleotide Excision Repair Is Dependent on UVC Fluence to Cells
Bibliographic record
Abstract
There is conflicting evidence for the role of the mismatch repair (MMR) genes hMLH1 and hMSH2 in the transcription-coupled repair (TCR) pathway of nucleotide excision repair. In the present work, we have examined the role of these MMR genes in nucleotide excision repair using two reporter gene assays. AdHCMVlacZ is a replication-deficient recombinant adenovirus that expresses the beta-galactosidase reporter gene under the control of the human cytomegalovirus immediate early promoter. We have reported previously a reduced host cell reactivation (HCR) for beta-galactosidase expression of UVC-irradiated AdHCMVlacZ in TCR-deficient Cockayne syndrome (CS) fibroblasts compared with normal fibroblasts, indicating that HCR depends, at least in part, on TCR. In addition, we have reported that UVC-enhanced expression of the undamaged reporter gene is induced at lower UVC fluences to cells and at higher levels after low UVC fluences in TCR-deficient compared with normal human fibroblasts, suggesting that persistent damage in active genes triggers increased activity from the human cytomegalovirus-driven reporter construct. We have examined HCR and UV-enhanced expression of the reporter gene in hMLH1-deficient HCT116 human colon adenocarcinoma cells and HCT116-chr3 cells (the MMR-proficient counterpart of HCT116) as well as hMSH2-deficient LoVo human colon adenocarcinoma cells and their hMSH2-proficient counterpart SW480 cells. We show a greater UV-enhanced expression of the undamaged reporter gene after low UVC exposure in HCT116 compared with HCT116-chr3 cells and in LoVo compared with SW480 cells. We show also a reduced HCR in HCT116 compared with HCT116-chr3 cells and in LoVo compared with SW480 cells. However, the reduction in HCR was less or absent when cells were pretreated with UVC. These results suggest that detection of an involvement of hMLH1 and hMSH2 in TCR is dependent on UVC (254 nm) fluence to cells.
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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) | 0.001 | 0.000 |
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".