17 Aug 3D Structure of Crucial DNA Repair Enzyme Resolved
MedicalResearch.com Interview with:
Professor Aneel K Aggarwal, PhD
Pharmacological Sciences and Oncological Sciences
Icahn School of Medicine at Mount Sinai
MedicalResearch.com: What is the background for this study?
Response: DNA polymerase ζ (Pol ζ) is the crucial enzyme that allows cells to cope with DNA damage resulting from exposure to environmental and industrial carcinogens and to other daily genotoxic stresses. At the same time, Pol ζ has emerged as an important target for discovery of therapeutics in the treatment of chemotherapy-resistant cancers.
MedicalResearch.com: What are the main findings?
Response: We have succeeded in resolving the 3-D atomic structure of the complete Pol ζ enzyme using cryo-electron microscopy.
MedicalResearch.com: What should readers take away from your report?
Response: With the structure in hand, we are able to address longstanding questions of how this complex enzyme protects cells against against DNA damage, and we provide a new framework for the design of drugs against cancers that are refractory to conventional chemotherapy.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: We hope that scientists will be able to structural information we have derived to test new hypotheses on the replication of damaged DNA and be able to develop new drugs against a number of cancers that become resistant to conventional chemotherapy.
MedicalResearch.com: Is there anything else you would like to add?
Response: As with any project of this magnitude, this was a team effort, and it was the culmination of a decade long effort by Dr. Radhika Malik, a remarkably talented senior scientist in my lab. We also enjoyed great collaborations with colleagues at the University of Texas Medical Branch and at the Instituto Biofisika in Spain, as well as a partnership with the Simon’s Electron Microscopy Center in New York.
Malik, R., Kopylov, M., Gomez-Llorente, Y. et al. Structure and mechanism of B-family DNA polymerase ζ specialized for translesion DNA synthesis. Nat Struct Mol Biol (2020). https://doi.org/10.1038/s41594-020-0476-7
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