Telosome, a mammalian telomere-associated complex formed by multiple telomeric proteins.
In mammalian cells, telomere-binding proteins TRF1 and TRF2 play crucial roles in telomere biology. They interact with several other telomere regulators including TIN2, PTOP, POT1, and RAP1 to ensure proper maintenance of telomeres. TRF1 and TRF2 are believed to exert distinct functions. TRF1 forms a complex with TIN2, PTOP, and POT1 and regulates telomere length, whereas TRF2 mediates t-loop formation and end protection. However, whether cross-talk occurs between the TRF1 and TRF2 complexes and how the signals from these complexes are integrated for telomere maintenance remain to be elucidated. Through gel filtration and co-immunoprecipitation experiments, we found that TRF1 and TRF2 are in fact subunits of a telomere-associated high molecular weight complex (telosome) that also contains POT1, PTOP, RAP1, and TIN2. We demonstrated that the TRF1-interacting protein TIN2 binds TRF2 directly and in vivo, thereby bridging TRF2 to TRF1. Consistent with this multi-protein telosome model, stripping TRF1 off the telomeres by expressing tankyrase reduced telomere recruitment of not only TIN2 but also TRF2. These results help to unify previous observations and suggest that telomere maintenance depends on the multi-subunit telosome.
Liu
Dan
D
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA. danl@bcm.tmc.edu
O'Connor
Matthew S
MS
Qin
Jun
J
Songyang
Zhou
Z
D015153:Blotting, Western; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D019084:Fluorescent Antibody Technique, Indirect; D017353:Gene Deletion; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D013058:Mass Spectrometry; D008856:Microscopy, Fluorescence; D046912:Multiprotein Complexes; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D000089804:Shelterin Complex; D038501:Tankyrases / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000502:physiology; D035321:Telomeric Repeat Binding Protein 1 / Q000502:physiology; D035341:Telomeric Repeat Binding Protein 2 / Q000502:physiology; D020827:rap1 GTP-Binding Proteins / Q000502:physiology
D046912:Multiprotein Complexes; D000089804:Shelterin Complex; D038501:Tankyrases; D034501:Telomere-Binding Proteins; D035321:Telomeric Repeat Binding Protein 1; D035341:Telomeric Repeat Binding Protein 2; D020827:rap1 GTP-Binding Proteins; C495876:ACD protein, human; C440849:POT1 protein, human; C440868:TINF2 protein, human; C418109:TNKS protein, human