zebrafish as a model system to study the physiological function of telomeric protein tpp1斑马鱼作为模型系统研究端粒的蛋白质tpp1的生理功能.pdf

Zebrafish as a Model System to Study the Physiological Function of Telomeric Protein TPP1 2 2 2 1 Yiying Xie , Dong Yang , Quanyuan He , Zhou Songyang * 1 State Key laboratory for Biocontrol, Sun Yat-Sen University, Guangzhou, People’s Republic of China, 2 Verna and Marrs McLean Department of Biochemistry and Molecular biology, Baylor College of Medicine, Houston, Texas, United States of America Abstract Telomeres are specialized chromatin structures at the end of chromosomes. Telomere dysfunction can lead to chromosomal abnormalities, DNA damage responses, and even cancer. In mammalian cells, a six-protein complex (telosome/shelterin) is assembled on the telomeres through the interactions between various domain structures of the six telomere proteins (POT1, TPP1, TIN2, TRF1, TRF2 and RAP1), and functions in telomere maintenance and protection. Within the telosome, TPP1 interacts directly with POT1 and TIN2 and help to mediate telosome assembly. Mechanisms of telomere regulation have been extensively studied in a variety of model organisms. For example, the physiological roles of telomere-targeted proteins have been assessed in mice through homozygous inactivation. In these cases, early embryonic lethality has prevented further studies of these proteins in embryogenesis and development. As a model system, zebrafish offers unique advantages such as genetic similarities with human, rapid developmental cycles, and ease of manipulation of its embryos. In this report, we detailed the identification of zebrafish homologues of TPP1, POT1, and TIN2, and showed that the domain structures and interactions of these telosome components appeared intact in zebrafish. Importantly, knocking down TPP1 led to multiple abnorma