Human SMC4 (Structural maintenance of chromosomes protein 4) ELISA Kit

The structural maintenance of chromosomes (SMC) family of proteins play essential roles in genomic stability. SMC heterodimers are required for sister-chromatid cohesion (Cohesin: Smc1 & Smc3), chromatin condensation (Condensin: Smc2 & Smc4), and DNA repair ( Smc5 & Smc6). The SMC heterodimers do not function alone and must associate with essential non-SMC subunits. To gain further insight into the essential and DNA repair roles of the Smc5-6 complex, we have purified fission yeast Smc5 and identified by mass spectrometry the co-precipitating proteins, Nse1 and Nse2. We show that both Nse1 and Nse2 interact with Smc5 in vivo, as part of the Smc5-6 complex. Nse1 and Nse2 are essential proteins and conserved from yeast to man. Loss of Nse1 and Nse2 function leads to strikingly similar terminal phenotypes to those observed for Smc5-6 inactivation. In addition, cells expressing hypomorphic alleles of Nse1 and Nse2 are, like Smc5-6 mutants, hypersensitive to DNA damage. Epistasis analysis suggests that like Smc5-6, Nse1, and Nse2 function together with Rhp51 in the homologous recombination repair of DNA double strand breaks. The results of this study strongly suggest that Nse1 and Nse2 are novel non-SMC subunits of the fission yeast Smc5-6 DNA repair complex.

The presented paper reviews the latest literature data on SMCs proteins (Structural Maintenance of Chromosomes) which contribute to regular chromatid segregation in mitosis and meiosis. SMC proteins are high molecular weight proteins with ATPase activity. These proteins are highly conserved in eukaryotes and prokaryotes. The structure of SMCs proteins is very specific, each SMC subunit contais two globular domains and a helical domain, called arm. Conservative motifs Walker A and Walker B are located at the N-terminal and C-terminal ends of the head domain. ATP binds to Walker A and Walker B of one subunit and the C-motif of the second subunit. C-motif is a part of C-terminal domain. SMCs can be classified into subfamilies, which associate with one another in particular pairs to perform their specific functions. SMCs are crucial components of condensins and cohesins. A single condensin or cohesin particle is composed of SMCs heterodimer and 3 or 2 non-SMC proteins, respectively. Cohesins are four-subunit complexes MCD1/RAD21/SCC1, SMC1, SMC3 i SCC3/SA1/SA2. The role of cohesins is holding sister chromatids together during mitosis and meiosis. They consists of SMC1-SMC3 heterodimer and Scc1 subunit which connects the head domains of SMC1 and SMC3, altogether forming a tripartite ring-like structure. Two models for the action of cohesin were proposed. One of them is referred as an embrace model. According to this cohesin complexes embrace two DNA duplexes to hold the sister chromatids together until metaphase. Proteolytic cleavage of See I by separase at the start of anaphase opens the ring and release two sister chromatids. Condensins play key role in chromosomes condensation. They are five-subunit complexes containing SMC2-SMC4 heterodimer. This constitues the core of two types of condensin complexes, condensin I and condensin It. The condensin II associates with chromatin in prophase. Condensin I is cytoplasmic and interact with chromosomes after nuclear envelope breakdown. Condensin It is required for chromosome condensation in early prophase, whereas condensin I is required for the complete dissociation of cohesin from chromosome arms, for chromosome compaction and for normal timing of progression through metaphase. Therefore both types are essential for proper chromosome segregation. Except for condensines and cohesines, there are other proteins which are important in chromosome segregation. Another protein required for proper chromosome segregation is SUMO. The SUMO is small ubiquitin related modifier is a member ubiquitin-like protein family. SUMO is engaged in cyclosome regulation. Cyclosome (APC/C-Anaphase Promoting Complex/Cyclosom), causes degradation of securine, which release separase and affect the conformation of Pds5 protein setting free cohesins. CENP-F is a facultative centromeric protein, which in cooperation with