A role for Drosophila SMC4 in the resolution of sister chromatids in mitosis

Background: Faithful segregation of the genome during mitosis requires inte rphase chromatin to be condensed into well-defined chromosomes, Chromosome condensation involves a multiprotein complex known as condensin that associ ates with chromatin early in prophase. Until now, genetic analysis of SMC s ubunits of the condensin complex in higher eukaryotic cells has not been pe rformed, and consequently the detailed contribution of different subunits t o the formation of mitotic chromosome morphology is poorly understood. Results: We show that the SMC4 subunit of condensin is encoded by the essen tial gluon locus in Drosophila. DmSMC4 contains all the conserved domains p resent in other members of the structural-maintenance-of-chromosomes protei n family. DmSMC4 is both nuclear and cytoplasmic during interphase, concent rates on chromatin during prophase, and localizes to the axial chromosome c ore at metaphase and anaphase. During decondensation in telophase, most of the DmSMC4 leaves the chromosomes. An examination of gluon mutations indica tes that SMC4 is required for chromosome condensation and segregation durin g different developmental stages. A detailed analysis of mitotic chromosome structure in mutant cells indicates that although the longitudinal axis ca n be shortened normally, sister chromatid resolution is strikingly disrupte d. This phenotype then leads to severe chromosome segregation defects, chro mosome breakage, and apoptosis. Conclusions: Our results demonstrate that SMC4 is critically important for the resolution of sister chromatids during mitosis prior to anaphase onset; (C) 2001 Elsevier Science Ltd. Ail rights reserved.