HUMAN AUTOANTIBODIES REVEAL TITIN AS A CHROMOSOMAL PROTEIN

Assembly of the higher-order structure of mitotic chromosomes is a pre requisite for proper chromosome condensation, segregation and integrit y. Understanding the details of this process has been limited because very few proteins involved in the assembly of chromosome structure hav e been discovered. Using a human autoimmune scleroderma serum that ide ntifies a chromosomal protein in human cells and Drosophila embryos, w e cloned the corresponding Drosophila gene that encodes the homologue of vertebrate titin based on protein size, sequence similarity, develo pmental expression and subcellular localization. Titin is a giant sarc omeric protein responsible for the elasticity of striated muscle that may also function as a molecular scaffold for myofibrillar assembly. M olecular analysis and immunostaining with antibodies to multiple titin epitopes indicates that the chromosomal and muscle forms of titin may vary in their NH2 termini. The identification of titin as a chromosom al component provides a molecular basis for chromosome structure and e lasticity.