The DNA repair function of<i>CUX1</i>contributes to radioresistance
Bibliographic record
Abstract
// Zubaidah M. Ramdzan 1 , Vasudeva Ginjala 3, * , Jordan B. Pinder 4, * , Dudley Chung 4, * , Caroline M. Donovan 1, 2, * , Simran Kaur 1, 2 , Lam Leduy 1 , Graham Dellaire 4 , Shridar Ganesan 3 , Alain Nepveu 1, 2, 3, 4 1 Goodman Cancer Research Centre, McGill University, Montreal, Quebec, H3A 1A3, Canada 2 Department of Biochemistry, McGill University, Montreal, Quebec, H3A 1A3, Canada 3 Department of Medicine, McGill University, Montreal, Quebec, H3A 1A3, Canada 4 Department of Oncology, McGill University, Montreal, Quebec, H3A 1A3, Canada * These authors contributed equally to this work Correspondence to: Alain Nepveu, email: alain.nepveu@mcgill.ca Keywords: CUX1, OGG1, base excision repair, radioresistance Received: March 30, 2016 Accepted: January 19, 2017 Published: January 28, 2017 ABSTRACT Ionizing radiation generates a broad spectrum of oxidative DNA lesions, including oxidized base products, abasic sites, single-strand breaks and double-strand breaks. The CUX1 protein was recently shown to function as an auxiliary factor that stimulates enzymatic activities of OGG1 through its CUT domains. In the present study, we investigated the requirement for CUX1 and OGG1 in the resistance to radiation. Cancer cell survival following ionizing radiation is reduced by CUX1 knockdown and increased by higher CUX1 expression. However, CUX1 knockdown is sufficient by itself to reduce viability in many cancer cell lines that exhibit high levels of reactive oxygen species (ROS). Consequently, clonogenic results expressed relative to that of non-irradiated cells indicate that CUX1 knockdown confers no or modest radiosensitivity to cancer cells with high ROS. A recombinant protein containing only two CUT domains is sufficient for rapid recruitment to DNA damage, acceleration of DNA repair and increased survival following radiation. In agreement with these findings, OGG1 knockdown and treatment of cells with OGG1 inhibitors sensitize cancer cells to radiation. Together, these results validate CUX1 and more specifically the CUT domains as therapeutic targets.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".