Reference number : GC-2017-Q1-02255, amendment number : , agreement type : G, recipient legal name : Cobb, Jennifer (University of Calgary), recipient country : CA, recipient province : nan, recipient city : Alberta, recipient postal code : nan, program name english : Discovery Grants Program - Individual, program name french : Programme de subventions à la découverte - individuelles, program purpose english : Structural maintenance of chromosomes (SMC) proteins form ring-like structures that interact with the genome to organize and restrict its movement. In eukaryotes, there are six different SMC proteins forming the core of three distinct heterodimeric complexes including 1. Cohesin (Smc1/Smc3), 2. Condensin (Smc2/Smc4), and 3. The Smc5/6 complex (Smc5/Smc6). SMC protein complexes are central to the process of how DNA is systematically packaged. Cohesin regulates sister chromatid cohes ion after replication and condensin drives chromosome packaging and condensation as cells go into mitosis. In contrast, most work on Smc5/6 has been primarily performed in the context of homologous recombination (HR) and DNA repair. Emerging work from our lab recently showed that Smc5/6 also has a function in chromatin association with the nuclear periphery and in maintaining higher-order chromatin structure at telomeres. 
Chromosomes are organized in the nucleus and locate to preferred positions. The nuclear envelope has a central role in this process and is critical for maintaining the architecture of the genome. The nuclear periphery is a region inhibitory to recombination. Cohesin and condensin are involved in the spatial organization of the nucleus, however a role for Smc5/6 in nuclear organization has not been addressed. This is surprising because Smc5/6 binds to repeats in the genome including telomeres and the rDNA that localize to the nuclear periphery. Characterization of Smc5/6 in tethering chromatin at the periphery will provide a clearer understanding of how the complex functions to down-regulate inappropriate homologous recombination. 
 Our central hypothesis: Smc5/6 binds repetitive elements such as telomeres and the rDNA localizing them to the nuclear periphery through interactions with inner nuclear membrane (INM) proteins. Our objectives for the current proposal include: 
 
 Objective 1: Determine whether Smc5/6 has a role in tethering telomeres at the periphery. We will determine whether Smc5/6 is important for telomere interactions and tethering to Mps3. 
 Objective 2: Examine the role of Smc5/6 in tethering the rDNA at the periphery. We will determine whether the localization of Smc5/6 at the rDNA is important for tethering repetitive elements to Heh1 and Nur1., program purpose french : Structural maintenance of chromosomes (SMC) proteins form ring-like structures that interact with the genome to organize and restrict its movement. In eukaryotes, there are six different SMC proteins forming the core of three distinct heterodimeric complexes including 1. Cohesin (Smc1/Smc3), 2. Condensin (Smc2/Smc4), and 3. The Smc5/6 complex (Smc5/Smc6). SMC protein complexes are central to the process of how DNA is systematically packaged. Cohesin regulates sister chromatid cohes ion after replication and condensin drives chromosome packaging and condensation as cells go into mitosis. In contrast, most work on Smc5/6 has been primarily performed in the context of homologous recombination (HR) and DNA repair. Emerging work from our lab recently showed that Smc5/6 also has a function in chromatin association with the nuclear periphery and in maintaining higher-order chromatin structure at telomeres. 
Chromosomes are organized in the nucleus and locate to preferred positions. The nuclear envelope has a central role in this process and is critical for maintaining the architecture of the genome. The nuclear periphery is a region inhibitory to recombination. Cohesin and condensin are involved in the spatial organization of the nucleus, however a role for Smc5/6 in nuclear organization has not been addressed. This is surprising because Smc5/6 binds to repeats in the genome including telomeres and the rDNA that localize to the nuclear periphery. Characterization of Smc5/6 in tethering chromatin at the periphery will provide a clearer understanding of how the complex functions to down-regulate inappropriate homologous recombination. 
 Our central hypothesis: Smc5/6 binds repetitive elements such as telomeres and the rDNA localizing them to the nuclear periphery through interactions with inner nuclear membrane (INM) proteins. Our objectives for the current proposal include: 
 
 Objective 1: Determine whether Smc5/6 has a role in tethering telomeres at the periphery. We will determine whether Smc5/6 is important for telomere interactions and tethering to Mps3. 
 Objective 2: Examine the role of Smc5/6 in tethering the rDNA at the periphery. We will determine whether the localization of Smc5/6 at the rDNA is important for tethering repetitive elements to Heh1 and Nur1., agreement title english : The role of the Smc5/6 complex in nuclear organization, agreement title french : The role of the Smc5/6 complex in nuclear organization, agreement number : RGPIN, agreement value : 200000.0, agreement start date : 2017-05-10, agreement end date : nan, description english : nan, description french : nan, expected results english : nan, expected results french : nan, additional information english : Grant or Award spanning more than one fiscal year. (2017-2018 to 2022-2023), additional information french : Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier. (2017-2018 à 2022-2023), owner organization : nserc-crsng, owner organization title : Natural Sciences and Engineering Research Council of Canada | Conseil de recherches en sciences naturelles et en génie du Canada