D-Titin: a giant protein with dual roles in chromosomes and muscles.
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 NH(2)-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.
Machado
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Department of Cell Biology and Anatomy, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA.
Andrew
D J
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D000818:Animals; D002459:Cell Fusion; D002842:Chromatids / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019457:Chromosome Breakage / Q000235:genetics; D020090:Chromosome Segregation; D002875:Chromosomes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D064211:Connectin; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008938:Mitosis / Q000235:genetics; D008970:Molecular Weight; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009132:Muscles / Q000737:chemistry* / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012518:Sarcomeres / Q000737:chemistry / Q000378:metabolism
D002868:Chromosomal Proteins, Non-Histone; D064211:Connectin; D029721:Drosophila Proteins; D019476:Insect Proteins; D009124:Muscle Proteins; C577347:sls protein, Drosophila; D011494:Protein Kinases