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UTMB-CET: Prakash Team Publishes in Nature

Drs. Satya and Louise Prakash of the University of Texas Medical Branch Center in Environmental Toxicology, in a long standing collaboration with Dr. Aneel Aggarwal at the Mount Sinai School of Medicine, recently demonstrated how DNA polymerase η (Polη) can promote error-free of bypass a common DNA lesion. Their findings were published in the June 24th, 2010 issue of Nature.

DNA polymerases mediate DNA replication and repair. DNA polymerase η (Polη), a member of the Y family of polymerases, is responsible for accurate DNA-lesion bypass of ultraviolet light-induced thymine dimers. Inactivation of Polη results in a variant form of xeroderma pigmentosum responsible for UV-induced skin cancer.  Structural studies demonstrated that the Polη active site is uniquely adapted to accomodate the thymine dimers, akin to the conformation found with undamaged B-DNA. Biochemical and genetic studies with the key residues in the Polη active site revealed that Glutamine-55 and Arginine-73 are important in maintaining adjacent thymines in a stable configuration, irrespective of whether or not the DNA is damaged. The structural and functional evidence provides an elegant rationale for how Polη can replicate efficiently through a thymine dimer lesion thus suppressing the mutagenic and carcinogenic consequences of sun exposure in humans.

DNA lesion-bypass illustration

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