February 24, 2020
Cancer biology investigator featured in Biochemistry and Molecular Biophysics seminar
Submitted by Biochemistry and Molecular Biophysics
Bret Freudenthal, professor of biochemistry and molecular biology at the 1xbet online games login of Kansas Medical Center and investigator at the 1xbet online games login of Kansas Cancer Center, is the featured speaker for the upcoming Biochemistry and Molecular Biophysics Seminar on Wednesday, Feb. 26. He will present "Mechanisms of nucleotide selection by telomerase: Implications for cancer therapy" at 4 p.m. in 120 Ackert Hall.
1xbet online games login protects genomic DNA by extending the protective telomere sequences found at chromosomal ends. How the 1xbet online games login active site selects canonical matched deoxyribonucleotides for telomere extension is poorly understood. To elucidate this mechanism, we determined the X-ray crystal structures of the catalytic subunit of a homolog to human 1xbet online games login reverse transcriptase, or TERT, throughout its entire catalytic cycle, including a complex poised to insert an incoming nucleotide into a telomeric sequence. Combining these structures with pre-steady-state kinetic analysis, we have assigned mechanistic roles for key active site residues with regard to 1xbet online games login fidelity and ribonucleotide insertion. Our observations with the model TERT were recapitulated in complementary studies with human 1xbet online games login to identify the 1xbet online games login steric gate residue that prevents the insertion of ribonucleotides in telomeres. From this we have obtained an understanding of how 1xbet online games login specifically selects canonical rather than noncanonical nucleotides for telomeric DNA elongation, thus protecting telomere integrity.