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Published online 30 October 2000. doi:10.1083/jcb.151.3.639
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© The Rockefeller University Press, 0021-9525/2000//639 $5.00
The Journal of Cell Biology, Volume 151, Number 3, , 2000 639-652

Original Article

D-Titin

: A Giant Protein with Dual Roles in Chromosomes and Muscles



Cristina Machadoa and Deborah J. Andrewa

a Department of Cell Biology and Anatomy, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196
Department of Cell Biology and Anatomy, The Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205-2196.410-955-4129410-614-2722

Previously, we reported that chromosomes contain a giant filamentous protein, which we identified as titin, a component of muscle sarcomeres. Here, we report the sequence of the entire titin gene in Drosophila melanogaster, D-Titin, and show that it encodes a two-megadalton protein with significant colinear homology to the NH2-terminal half of vertebrate titin. Mutations in D-Titin cause chromosome undercondensation, chromosome breakage, loss of diploidy, and premature sister chromatid separation. Additionally, D-Titin mutants have defects in myoblast fusion and muscle organization. The phenotypes of the D-Titin mutants suggest parallel roles for titin in both muscle and chromosome structure and elasticity, and provide new insight into chromosome structure.

Key Words: chromosome condensation • Drosophila melanogaster • myoblast fusion • sarcomere • titin

© 2000 The Rockefeller University Press

Abbreviations used in this paper: FISH, fluorescence in situ hybridization; FN3, fibronectin type 3; MDa, megadalton; nt, nucleotide; ORF, open reading frame; SMC, structural maintenance of chromosome; topo II, topoisomerase II.


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