A role for Drosophila SMC4 in the resolution of sister chromatids in mitosis.
BACKGROUND
Faithful segregation of the genome during mitosis requires interphase chromatin to be condensed into well-defined chromosomes. Chromosome condensation involves a multiprotein complex known as condensin that associates with chromatin early in prophase. Until now, genetic analysis of SMC subunits of the condensin complex in higher eukaryotic cells has not been performed, and consequently the detailed contribution of different subunits to the formation of mitotic chromosome morphology is poorly understood.


RESULTS
We show that the SMC4 subunit of condensin is encoded by the essential gluon locus in Drosophila. DmSMC4 contains all the conserved domains present in other members of the structural-maintenance-of-chromosomes protein family. DmSMC4 is both nuclear and cytoplasmic during interphase, concentrates on chromatin during prophase, and localizes to the axial chromosome core at metaphase and anaphase. During decondensation in telophase, most of the DmSMC4 leaves the chromosomes. An examination of gluon mutations indicates that SMC4 is required for chromosome condensation and segregation during different developmental stages. A detailed analysis of mitotic chromosome structure in mutant cells indicates that although the longitudinal axis can be shortened normally, sister chromatid resolution is strikingly disrupted. This phenotype then leads to severe chromosome segregation defects, chromosome breakage, and apoptosis.


CONCLUSIONS
Our results demonstrate that SMC4 is critically important for the resolution of sister chromatids during mitosis prior to anaphase onset.
Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto 4150, Portugal.
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S
Steffensen
P A
PA
Coelho
N
N
Cobbe
S
S
Vass
M
M
Costa
B
B
Hassan
S N
SN
Prokopenko
H
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Bellen
M M
MM
Heck
C E
CE
Sunkel
D000483:Alleles; D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000032:analysis; D002842:Chromatids / Q000502:physiology*; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002875:Chromosomes / Q000502:physiology; D003001:Cloning, Molecular; D004330:Drosophila / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D029721:Drosophila Proteins; D017344:Genes, Insect; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008938:Mitosis / Q000502:physiology*; D016296:Mutagenesis; D009474:Neurons / Q000502:physiology; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D013234:Stem Cells / Q000502:physiology
C103227:Barr protein, Drosophila; D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D029721:Drosophila Proteins; D019476:Insect Proteins; C409162:SMC4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins