Abstract
Structural maintenance of chromosome (SMC) proteins are key organizers of chromosome architecture and are essential for genome integrity. They act by binding to chromatin and connecting distinct parts of chromosomes together. Interestingly, their potential role in providing connections between chromatin and the mitotic spindle has not been explored. Here, we show that yeast SMC proteins bind directly to microtubules and can provide a functional link between microtubules and DNA. We mapped the microtubule-binding region of Smc5 and generated a mutant with impaired microtubule binding activity. This mutant is viable in yeast but exhibited a cold-specific conditional lethality associated with mitotic arrest, aberrant spindle structures, and chromosome segregation defects. In an in vitro reconstitution assay, this Smc5 mutant also showed a compromised ability to protect microtubules from cold-induced depolymerization. Collectively, these findings demonstrate that SMC proteins can bind to and stabilize microtubules and that SMC-microtubule interactions are essential to establish a robust system to maintain genome integrity.
Highlights
Structural maintenance of chromosome (SMC) proteins organize chromosome architecture, whereas microtubules form the structural framework for chromosome movement in mitosis
We show that yeast SMC proteins bind directly to microtubules and can provide a functional link between microtubules and DNA
In an in vitro reconstitution assay, this Smc5 mutant showed a compromised ability to protect microtubules from cold-induced depolymerization. These findings demonstrate that SMC proteins can bind to and stabilize microtubules and that SMC-microtubule interactions are essential to establish a robust system to maintain genome integrity
Summary
SMC proteins organize chromosome architecture, whereas microtubules form the structural framework for chromosome movement in mitosis. Structural maintenance of chromosome (SMC) proteins are key organizers of chromosome architecture and are essential for genome integrity They act by binding to chromatin and connecting distinct parts of chromosomes together. H. K.), Canadian Cancer Society Research Institute Grant 020304 The Institute for Research in Immunology and Cancer (IRIC) is supported in part by the Canadian Center of Excellence in Commercialization and Research (CECR), the Canada Foundation for Innovation, and Fonds de Recherche Sante (FRQS). Replicated sister chromatids must be connected to each other and reconfigured into highly condensed chromosomes to allow effective segregation in anaphase [1, 2] This reorganization of chromatin depends in large part on a family of proteins known as the structural maintenance of chromosome (SMC) proteins [2,3,4]. Given the biological significance of proteins linking microtubules and chromatin, we set out to determine whether SMC proteins interact directly with microtubules and to understand the potential roles and implications of these interactions in vivo
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