Telomeres, the natural ends of linear eukaryotic chromosomes, are essential for cell viability and genome integrity. Aberrations at telomeres have been implicated in cancer and aging. In mammalian cells, telomere repeat factors 1 and 2 (TRF1 and TRF2) are the first two identified telomere binding proteins that play essential roles in telomere homeostasis and maintenance. Both TRF1 and TRF2 contain a central TRF homology (TRFH) domain and a C-terminal DNA-binding Myb domain. TRF1 and TRF2 only contain one Myb domain and they achieve high affinity DNA association by dimerization via their TRFH domains. Fission yeast Schizosaccharomyces pombe Taz1 associates with telomeric dsDNAs and plays an important role in telomere length regulation and protection and has been considered as the functional ortholog of mammalian TRF proteins. However, the structural and functional mechanism of Taz1 in telomere protection and telomere length regulation remains unclear.
DENG Wei and her colleagues from a research group led by Prof. LEI Ming at National Center for Protein Science Shanghai, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, determine the crystal structures of central and dimerization domains of Taz1. Combined with the in vivo genetical results, their studies show that the central domain of Taz1 (Taz1HD) has a different 3D structure than the TRFH domains and does not contain a peptide-binding pocket found in mammalian TRFH-containing proteins. Unlike the TRFH domain of TRF proteins, Taz1H does not mediate the dimerization of Taz1. Instead, Taz1 utilizes a separate four-helix bundle (Taz1DD) to mediate the dimerization. Notably, similar to the case of TRF proteins, the dimerization plays an essential role in telomere localization of Taz1 and telomere length regulation. These results highlight the remarkable structural plasticity of functionally conserved telomere binding proteins; except for the DNA-binding activities, many important functions are preserved through structurally distinct modules of telomere binding proteins in different organisms.
This study entitled “Fission yeast telomere-binding protein Taz1 is a functional but not a structural counterpart of human TRF1 and TRF2” was published online in Cell Research on June 19, 2015. This work was supported by grants from the Ministry of Science and Technology of China, the National Natural Science Foundation of China, the Strategic Priority Research Program of the Chinese Academy of Sciences, and Howard Hughes Medical Institute.
Contact:
LEI Ming, Principal Investigator
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
Shanghai 200031, China.
Email: leim@sibcb.ac.cn
Appendix：
