Previously, we reported that chromosomes contain a giant filamentous protei
n, 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 i
n 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 phenot
ypes of the D-Titin mutants suggest parallel roles for titin in both muscle
and chromosome structure and elasticity, and provide new insight into chro
mosome structure.