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SMC5 and SMC6 genes are required for the segregation of repetitive chromosome regions

Nature Cell Biology volume 7, pages 412–419 (2005)Cite this article

Abstract

Structure chromosome (SMC) proteins organize the core of cohesin, condensin and Smc5–Smc6 complexes1. The Smc5–Smc6 complex is required for DNA repair, as well as having another essential but enigmatic function1. Here, we generated conditional mutants of SMC5 and SMC6 in budding yeast, in which the essential function was affected. We show that mutant smc5-6 and smc6-9 cells undergo an aberrant mitosis in which chromosome segregation of repetitive regions is impaired; this leads to DNA damage and RAD9-dependent activation of the Rad53 protein kinase. Consistent with a requirement for the segregation of repetitive regions, Smc5 and Smc6 proteins are enriched at ribosomal DNA (rDNA) and at some telomeres. We show that, following Smc5–Smc6 inactivation, metaphase-arrested cells show increased levels of X-shaped DNA (Holliday junctions) at the rDNA locus. Furthermore, deletion of RAD52 partially suppresses the temperature sensitivity of smc5-6 and smc6-9 mutants. We also present evidence showing that the rDNA segregation defects of smc5/smc6 mutants are mechanistically different from those previously observed for condensin mutants2,3. These results point towards a role for the Smc5–Smc6 complex in preventing the formation of sister chromatid junctions, thereby ensuring the correct partitioning of chromosomes during anaphase.

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Figure 1: Loss of Smc5–Smc6 function generates DNA damage following mitosis.
Figure 2: The Smc5–Smc6 heterodimer is enriched in nucleolar and telomeric regions and is required for nucleolar integrity during anaphase.
Figure 3: smc6-9 cells missegregate the centromere-distal rDNA flank and the telomere, but not regions immediately before the rDNA or closer to the centromere in chromosome XII.
Figure 4: smc6-9 cells missegregate telomere but not arm tags in chromosome V.
Figure 5: The Smc5–Smc6 complex is involved in processing X-shaped DNA intermediates.

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Acknowledgements

We are grateful to T. Tanaka, D. Moazed, K. Bloom, M. Yanagida, A. Verreault, J. Diffley, R. Rothstein and D. Toczyski for reagents, plasmids and strains; and K. Myant for help with the initial development of ts alleles. We also thank J. Diffley and S. Jackson for helpful advice. J.T.-R. was supported by the European Commission (Marie Curie Intra-European Fellowship). This work was supported by the Medical Research Council UK.

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Authors and Affiliations

  1. Cell Cycle Group, MRC Clinical Sciences Centre, Imperial College London, Du Cane Road, London, W12 0NN, UK

    Jordi Torres-Rosell, Félix Machín, Sarah Farmer, Adam Jarmuz & Luis Aragón

  2. Marie Curie Research Institute, The Chart, Oxted, RH8 0TL, Surrey, UK

    Trevor Eydmann & Jacob Z. Dalgaard

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  1. Jordi Torres-Rosell
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Correspondence to Luis Aragón.

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Supplementary figures S1, S2, S3 and S4; supplementary methods, and table S1 (PDF 400 kb)

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Torres-Rosell, J., Machín, F., Farmer, S. et al. SMC5 and SMC6 genes are required for the segregation of repetitive chromosome regions. Nat Cell Biol 7, 412–419 (2005). https://doi.org/10.1038/ncb1239

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