Dataset
Human DNA Cross-Link Repair 1A (DCLRE1A, SNM1A); A Target Enabling Package
- Documentation:
- A description of the materials and methods is included within the TEP datasheet. Cancer cells experience genomic instability, probably through a combination of excessive replicative activity and the loss of function of checkpoint and DNA repair pathways that may have contributed to the oncogenic transformation. Chemotherapy by DNA-damaging agents such as cisplatin and nitrogen mustards create DNA interstrand crosslinks (ICL), which can lead to double-strand breaks and cell death when the cells replicate their DNA. Genotoxic drugs are counteracted by the cell’s DNA damage response. Hence, it is expected that inhibiting DNA repair proteins would sensitise cells to chemotherapy. Here we address an enzyme that participates in the repair of ICLs, DCLRE1A. The TEP includes expression clones and methods for producing the catalytic domain and high-throughput activity assays. Furthermore, we provide a crystallization system that generates thousands of reproducible crystals that allow soaking of small-molecule ligands. We provide crystal structures of several small molecule fragments and inhibitors, opening the way to development of more potent and selective inhibitors.
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Access Document
- Files:
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(Preview, pdf, 1.3MB, Terms of use)
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Authors/Creators
Contributors
+ Gileadi, O
- Institution:
- University of Oxford
- Division:
- MSD
- Department:
- NDM
- Sub department:
- Structural Genomics Consortium
- Role:
- Principal Investigator (PI)
+ Aitkenhead, H
- Institution:
- University of Oxford
- Oxford college:
- Balliol College
- Role:
- Researcher
+ Lee, S
- Role:
- Researcher
+ McHugh, P
- Department:
- Oncology
- Role:
- Researcher
+ Schofield, C
- Institution:
- University of Oxford
- Division:
- MPLS
- Department:
- Chemistry
- Sub department:
- Organic Chemistry
- Role:
- Researcher
- Publisher:
- University of Oxford
- Publication date:
- 2018
- Keywords:
- Subjects:
- Pubs id:
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1480165
- UUID:
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uuid:334f0870-2042-44ad-b004-eab8dca8d09e
- Local pid:
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pubs:1480165
- Deposit date:
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2018-04-20
- ARK identifier:
Terms of use
- Copyright date:
- 2018
- Notes:
- This deposition represents version 2 of the TEP datasheet. Changes include, but are not limited to: Addition of hyperlinks throughout the body of the datasheet; Addition of Useful Links to relevant databases; Addition of a Reference box where applicable; Other modifications necessary for page spacing and visualisation. Please note, all data and results within the document remain the same as provided in version 1.
- Licence:
- ORA Terms and conditions
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