University of Pittsburgh Department of Biological Sciences Presents:
Dr. Jayakrishnan Nandakumar
Unviersity of Michigan
"Functions of telomeric shelterin proteins outside of their role in protecting chromosome ends"
Monday, April 23, 2018
169 Crawford Hall
10:50 A.M. refreshments
Host: Dr. Andrea Berman
Telomeres perform two essential functions at chromosome ends namely, chromosome end protection and chromosome end replication. In addition, telomeres also play a unique yet poorly understood role in cells undergoing meiosis. Tethering telomeres to the inner nuclear membrane (INM) allows for homologous chromosome pairing during meiosis. A meiosis-specific protein TERB1 binds the telomeric protein TRF1 to establish telomere-INM connectivity and is essential for mouse fertility. In this seminar I will describe the structure of the human TRF1-TERB1 interface that we recently solved to reveal the structural basis for telomere-INM linkage. I will also share new functional data that were inspired by this structure. In brief, we observed that disruption of the TRF1-TERB1 interface abrogates binding and compromises telomere-INM attachment in mice. An embedded CDK-phosphorylation site within the TRF1-binding region of TERB1 provides a mechanism for cap exchange, a late-pachytene phenomenon involving the dissociation of the TRF1-TERB1 complex. Indeed, further strengthening this interaction interferes with cap exchange. Finally, our biochemical analysis implicates distinct complexes for telomere-INM tethering and chromosome end protection during meiosis. Our studies unravel the structure, stoichiometry, and physiological implications underlying telomere-INM tethering, thereby providing unprecedented insights into the unique function of telomeres in meiosis.