Nat Struct and Mol Biol: Revealing how DNA polymerases ζ protect cells from DNA damage or hopefully help develop new treatments against drug-resistant cancers.

19, 2020 // -- In a recent study published in the international journal Nature Structural and Molecular Biology, scientists from Mount Sinai Hospital and other institutions revealed for the first time the 3-D structure and working mechanisms of complex enzymes that protect cells from persistent DNA damage. Or to provide new ideas for developing new treatments for chemotherapy-resistant cancer, the researchers describe how they used advanced cryoscopic technology to reveal detailed structural information about DNA polymerase ζ (Pol ζ), the structure and mechanism of DNA polymerase ζ that have been a mystery to scientists for years.
Photo Source: CC0 Public Domain researcher Professor Anel Aggarwal says parsing the structure of the complete Pol ζ enzyme at near-atomic resolution may help researchers solve a long-standing problem of how this particular polymerase replicates through everyday DNA damage events, while also providing researchers with a template to design new drugs for cancers that traditional chemotherapy cannot cure.
DNA polymeraseζ is a very important enzyme that helps cells fight more than 100,000 DAILY DNA injuries, often from normal metabolic activity and environmental violations such as ultraviolet light, ionizing radiation, and industrial carcinogens. In the
article, the researchers reveal how the enzyme protects cells from natural and man-made environments and cellular stress through a fine and complex structure made up of four different proteins that can be connected by a glycogen or chrysanthemum-like structure that could help researchers develop drugs that inhibit the function of DNA polymerases to treat cancer types that are resistant to chemotherapy, such as non-small cell lung cancer, prostate cancer and ovarian cancer.
the causes of cancer resistance to chemotherapy such as cisplatin actually depend on the DNA damage effects of cancer cells, the function of blocking or suppressing DNA polymerases ζ may make cancer cells sensitive again to the therapeutic effects of chemotherapy.
researcher Aggarwal explains that the development of effective inhibitors is often hampered by previous researchers' inability to clearly parse the structural information of DNA polymerase ζ, and that we have observed a clear picture in this study, and that the results may also help researchers develop more effective treatments that could help develop new treatments that effectively overcome resistance in cancer patients for thousands of cancer patients who are resistant to chemotherapy.
In the end, researchers say researchers have not been able to make significant progress for years, mainly because they have not been able to obtain detailed structural information about DNA polymerases ζ, a problem they solved using cryoenthescopic technology, and because they have imaged fast-frozen molecules in solutions, high-resolution imaging of complex molecules may lead to future research advances that could revolutionized the entire field of structural biology.
() Original source: Malik, R., Kopylov, M., Gomez-Llorente, Y. et al. Structure and mechanism of B-family DNA polymerase ζ for translesion DNA synthesis. Nat Struct Mol Biol (2020). doi:10.1038/s41594-020-0476-7.