title: SMC5 and MMS21 are required for chromosome cohesion and mitotic progression.
abstract: Members of the structural maintenance of chromosome (SMC) protein family have essential functions during mitosis, ensuring chromosome condensation (SMC2/4) and cohesion (SMC1/3). The SMC5/6 complex has been implicated in a variety of DNA maintenance processes but unlike the other SMC proteins, SMC5/6 have not been attributed any role in mitosis. Here, we find that ablation of either SMC5 or the SUMO-ligase MMS21 leads to premature sister chromatid separation prior to anaphase. The failure of normal chromosome alignment activates the spindle assembly checkpoint and blocks mitotic progression. Interestingly, there is no similar mitotic response to ablation of SMC6. Further, we show that mitotic SMC5 co-elutes from column fractions that contain MMS21 but lack SMC6. Our results thus establish that SMC5 is crucial for mitotic progression and maintenance of sister chromatid cohesion during mitosis, and that this role of SMC5 seems to be independent of the SMC5/6 complex.
authors.affiliation: Institut de Biologie Structurale (CEA, CNRS, UJF), Grenoble, France. SBehlke@gmail.com
authors.forename: Susanne
authors.initials: S
authors.lastname: Behlke-Steinert
authors.forename: Leila
authors.initials: L
authors.lastname: Touat-Todeschini
authors.forename: Dimitrios A
authors.initials: DA
authors.lastname: Skoufias
authors.forename: Robert L
authors.initials: RL
authors.lastname: Margolis
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002842:Chromatids / Q000187:drug effects; D002868:Chromosomal Proteins, Non-Histone; D002869:Chromosome Aberrations; D020090:Chromosome Segregation; D006367:HeLa Cells; D006801:Humans; D008025:Ligases / Q000378:metabolism*; D008677:Metaphase; D008938:Mitosis; D010641:Phenotype; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D034741:RNA, Small Interfering; C432931:SMC5 protein, human; C432932:SMC6 protein, human; D008025:Ligases; C503501:NSMCE2 protein, human