Structural maintenance of chromosomes protein 5 is a protein encoded by the SMC5 gene in human. [5] [6]
The structural maintenance of chromosomes' complex underlying mechanisms involved in the dynamics of chromatin dynamics is unknown, and new discoveries are shedding light on the various functions. [7] The SMC complex mediates long-distance interactions that enable higher-order folding of chromatin in interphase. The SMC complex has an ATPase activity, a conserved kleisin, as well as regulatory subunits. [7] SMC protein complexes are involved in DNA repair, transcriptional pathways, regulation of chromosome segregation, and immunity in Arabidopsis. In eukaryotes the structural maintenance chromosomes consists of cohesin (SMC1 AND SMC3), condensin (SMC2 and SMC4), and SMC5/6 complexes.
The Smc5/6 complex was discovered in fission yeast. RAD18 (SMC6), the DNA damage gene in fission yeast, also encodes an SMC-like protein and forms a heterodimeric complex with Spr18 (SMC5) protein. [8] [9] In yeast, SMC5/6 complex has sub-units which consists of SMC5, SMC6 and six nonstructural maintenance of chromosomes (NSE) proteins. Nse1-Nse3-Nse4 subunits bridge the Smc5 head Smc6 and allow the binding of DNA. [10] [11] [12]
It is involved in the Alternative lengthening of telomeres cancer mechanism. [13] [14]
Nse1-Nse3-Nse4 subunits bridge the heads of the Smc5 and Smc6 proteins and allow the complex to bind DNA. Nse5 and Nse6 form a sub-complex which localizes to the head of the SMC5/6 complex in the budding yeast Saccharomyces cerevisiae , and to the hinges of the SMC5/6 complex in the fission yeast Schizosaccharomyces pombe . The Nse5/6 sub-complex is required for the replication of S. cerevisiae, but has not been characterized as essential in S. pombe. Orthologous proteins to Nse5-Nse6 exist in other eukaryotes, namely ASAP1-SNI1 in Arabidopsis thaliana and SLF1-SLF2 in humans, which are believed have similar function to their Nse counterparts. The localization of SLF1 and SLF2 on the human SMC5/6 complex is unknown. [15] [16]
The Smc5/6 complex has localization methods which are not heavily conserved. In humans the complex is localized to viral DNA sequences using SMC5/6 localization factors 1 and 2 (SLF1 and SLF2) which contributes to viral resistance. [17] In the plant A. thaliana, this heterodimer can be localized to double stranded breaks for homologous recombination using the SWI3B complex of the SWI/SNF pathway. [18] Once localized to the DNA, the SCM5/6 complex non-specifically binds to ~20 DNA base pairs [19]
Smc5 and Smc6 proteins form a heterodimeric ring-like structure and, together with other non-SMC elements, form the SMC-5/6 complex. In the worm Caenorhabditis elegans this complex interacts with the HIM-6(BLM) helicase to promote meiotic recombination intermediate processing and chromosome maturation. [20] The SMC-5/6 complex in mouse oocytes is essential for the formation of segregation competent bivalents during meiosis. [21] In humans, a chromosome breakage syndrome characterized by severe lung disease in early childhood is associated with a mutation in a component of the SMC-5/6 complex. [22] Patient's cells display chromosome rearrangements, micronuclei, sensitivity to DNA damage and defective homologous recombination.
Heterochromatin is a tightly packed form of DNA or condensed DNA, which comes in multiple varieties. These varieties lie on a continuum between the two extremes of constitutive heterochromatin and facultative heterochromatin. Both play a role in the expression of genes. Because it is tightly packed, it was thought to be inaccessible to polymerases and therefore not transcribed; however, according to Volpe et al. (2002), and many other papers since, much of this DNA is in fact transcribed, but it is continuously turned over via RNA-induced transcriptional silencing (RITS). Recent studies with electron microscopy and OsO4 staining reveal that the dense packing is not due to the chromatin.
Schizosaccharomyces pombe, also called "fission yeast", is a species of yeast used in traditional brewing and as a model organism in molecular and cell biology. It is a unicellular eukaryote, whose cells are rod-shaped. Cells typically measure 3 to 4 micrometres in diameter and 7 to 14 micrometres in length. Its genome, which is approximately 14.1 million base pairs, is estimated to contain 4,970 protein-coding genes and at least 450 non-coding RNAs.
Condensins are large protein complexes that play a central role in chromosome assembly and segregation during mitosis and meiosis. Their subunits were originally identified as major components of mitotic chromosomes assembled in Xenopus egg extracts.
The spindle checkpoint, also known as the metaphase-to-anaphase transition, the spindle assembly checkpoint (SAC), the metaphase checkpoint, or the mitotic checkpoint, is a cell cycle checkpoint during mitosis or meiosis that prevents the separation of the duplicated chromosomes (anaphase) until each chromosome is properly attached to the spindle. To achieve proper segregation, the two kinetochores on the sister chromatids must be attached to opposite spindle poles. Only this pattern of attachment will ensure that each daughter cell receives one copy of the chromosome. The defining biochemical feature of this checkpoint is the stimulation of the anaphase-promoting complex by M-phase cyclin-CDK complexes, which in turn causes the proteolytic destruction of cyclins and proteins that hold the sister chromatids together.
Subtelomeres are segments of DNA between telomeric caps and chromatin.
SMC complexes represent a large family of ATPases that participate in many aspects of higher-order chromosome organization and dynamics. SMC stands for Structural Maintenance of Chromosomes.
The replication factor C, or RFC, is a five-subunit protein complex that is required for DNA replication.
Cohesin is a protein complex that mediates sister chromatid cohesion, homologous recombination, and DNA looping. Cohesin is formed of SMC3, SMC1, SCC1 and SCC3. Cohesin holds sister chromatids together after DNA replication until anaphase when removal of cohesin leads to separation of sister chromatids. The complex forms a ring-like structure and it is believed that sister chromatids are held together by entrapment inside the cohesin ring. Cohesin is a member of the SMC family of protein complexes which includes Condensin, MukBEF and SMC-ScpAB.
Structural maintenance of chromosomes protein 1A (SMC1A) is a protein that in humans is encoded by the SMC1A gene. SMC1A is a subunit of the cohesin complex which mediates sister chromatid cohesion, homologous recombination and DNA looping. In somatic cells, cohesin is formed of SMC1A, SMC3, RAD21 and either SA1 or SA2 whereas in meiosis, cohesin is formed of SMC3, SMC1B, REC8 and SA3.
Cell cycle checkpoint protein RAD1 is a protein that in humans is encoded by the RAD1 gene.
Double-strand-break repair protein rad21 homolog is a protein that in humans is encoded by the RAD21 gene. RAD21, an essential gene, encodes a DNA double-strand break (DSB) repair protein that is evolutionarily conserved in all eukaryotes from budding yeast to humans. RAD21 protein is a structural component of the highly conserved cohesin complex consisting of RAD21, SMC1A, SMC3, and SCC3 [ STAG1 (SA1) and STAG2 (SA2) in multicellular organisms] proteins, involved in sister chromatid cohesion.
Structural maintenance of chromosomes protein 3 (SMC3) is a protein that in humans is encoded by the SMC3 gene. SMC3 is a subunit of the Cohesin complex which mediates sister chromatid cohesion, homologous recombination and DNA looping. Cohesin is formed of SMC3, SMC1, RAD21 and either SA1 or SA2. In humans, SMC3 is present in all cohesin complexes whereas there are multiple paralogs for the other subunits.
Crossover junction endonuclease MUS81 is an enzyme that in humans is encoded by the MUS81 gene.
Wings apart-like protein homolog (WAPL) is a protein that in humans is encoded by the WAPAL gene. WAPL is a key regulator of the Cohesin complex which mediates sister chromatid cohesion, homologous recombination and DNA looping. Cohesin is formed of SMC3, SMC1, RAD21 and either SA1 or SA2. Cohesin has a ring-like arrangement and it is thought that it associates with the chromosome by entrapping it whether as a loop of DNA, a single strand or a pair of sister chromosomes. WAPL forms a complex with PDS5A or PDS5B and releases cohesin from DNA by opening the interface between SMC3 and RAD21.
Structural maintenance of chromosomes protein 4 (SMC-4) also known as chromosome-associated polypeptide C (CAP-C) or XCAP-C homolog is a protein that in humans is encoded by the SMC4 gene. SMC-4 is a core subunit of condensin I and II, large protein complexes involved in high order chromosome organization, including condensation and segregation. SMC-4 protein is commonly associated with the SMC-2 protein, another protein complex within the SMC protein family. SMC-4 dimerizes with SMC-2, creating the flexible and dynamic structure of the condensin holocomplex. An over-expression of the SMC-4 protein is shown to impact carcinogenesis.
Structural maintenance of chromosomes protein 6 is a protein that in humans is encoded by the SMC6 gene.
Meiotic recombination protein REC8 homolog is a protein that in humans is encoded by the REC8 gene.
Structural maintenance of chromosomes protein 2 (SMC-2), also known as chromosome-associated protein E (CAP-E), is a protein that in humans is encoded by the SMC2 gene. SMC2 is part of the SMC protein family and is a core subunit of condensin I and II, large protein complexes involved in chromosome condensation, overall organization. Several studies have demonstrated the necessity of SMC2 for cell division and proliferation.
Sister chromatid cohesion refers to the process by which sister chromatids are paired and held together during certain phases of the cell cycle. Establishment of sister chromatid cohesion is the process by which chromatin-associated cohesin protein becomes competent to physically bind together the sister chromatids. In general, cohesion is established during S phase as DNA is replicated, and is lost when chromosomes segregate during mitosis and meiosis. Some studies have suggested that cohesion aids in aligning the kinetochores during mitosis by forcing the kinetochores to face opposite cell poles.
Structural maintenance of chromosomes protein 1B (SMC-1B) is a protein that in humans is encoded by the SMC1B gene. SMC proteins engage in chromosome organization and can be broken into 3 groups based on function which are cohesins, condensins, and DNA repair.SMC-1B belongs to a family of proteins required for chromatid cohesion and DNA recombination during meiosis and mitosis. SMC1ß protein appears to participate with other cohesins REC8, STAG3 and SMC3 in sister-chromatid cohesion throughout the whole meiotic process in human oocytes.