The centromeres of eukaryotic chromosomes pair- and split-up recombinant chromosomes in mitosis and meiosis. The functional centromeres have been isolated and labeled in single-celled eukaryotes such as budding yeast (Saccharomyces cerevisiae) or fission yeast (Schizosaccharomyces pombe). Saccharomyces cerevisiae centromere(CEN) are 125 bp of DNA divided into three sections (CDEI, CDEII, and CDEIII).
Centromeres are part of the chromosomes that regulate mitotic and meiotic segregation and from which chromosomes latch onto centromere microtubules. Pericentromere (Physical area) - This area is where bidirectional sister centromeres have their geometry in metaphase. These special places are situated at the main constrictor of each chromosome and arranged into a unique chromatin arrangement. Centromere binding DNA proteins A, B, and C in humans (CENP-A, CENP-B, and CENP-C respectively). The DNA binding by CENP-A and CENP-C is neither sequence specific nor recurrent CENP-B is a centromeric DNA-binding protein that detects a 17-bp box (CENP-B) in centromeric satellite DNA of humans and mice.
Centromere protein B (CENP-B) is a centromeric DNA-binding protein conserved in many mammals and yeast. CENP-B was first cloned in human cells as an 80 kDa autoantigen that ACA patient sera recognized. CENP-B is present on centromeric heterochromatin in human chromosomes and might attach to a subtype of human alphoid satellite DNA. CENP-B was not clearly defined in non-primates and might therefore, in theory, be a primate-specific alphoid DNA-binding protein.
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DNA and Centromere Protein B
The primary contributing factor to the functional organization of the mammalian centromere or kinetochore is believed to be DNA. However, identifying the specific DNA segments responsible has proven challenging due to the difficulty of generating activity assays with mammalian cells. Research on human chromosome 21 DNA has revealed the long-range distribution of α-satellite DNA monomers containing the CENP-B box. These arrays, each exceeding 1 Mb and located adjacent to one another in the centromeric region, consist of α-satellite monomers, each featuring a CENP-B box. African green monkeys (AGM), which are phylogenetically closer to humans than mice, also possess a significant amount of α-satellite DNA. Furthermore, the AGM genome contains the recognition sequence for CENP-B within its satellite centromere DNA.
Fig. 1 Schematic diagram of the interaction between human centromere, DNA and CENP-B (Chardon, F.; et al. 2022).
Biology of Centromere Protein B
The CENP-B gene is directly involved in mitotic events such as chromosome positioning, segregation and cytokinesis. CENP-B coordinates centromere size, assembly, and spindle microtubule assembly to make sure chromosomes segregate as they should during mitosis.
Maintenance of Centromere Structure
CENP-B can bind to specific locations on the centromere, promoting structural repair and dynamic remodeling of the centromere.
Chromosome Segregation
Because CENP-B binds to other centromere proteins, it prevents chromosomes from being lost during mitosis and meiosis, ensuring that cells accurately transfer genetic material to daughter cells during division.
Regulation of Gene Expression
CENP-B may also regulate cellular physiology by influencing the expression of centromere genes. Additionally, during DNA repair processes, CENP-B can interact with other proteins to facilitate repair and maintain genomic integrity.
Because CENP-B is essential for cell division and maintaining genome stability, defects in the expression or function of this protein can lead to diseases, including cancer. Therefore, understanding the physiological role of CENP-B is crucial for cell biology and the development of targeted therapies.
Expression of Centromere Protein B in Cells
CENP-B is a nuclear protein typically located at the centromeres of chromosomes within cells. The expression of CENP-B can be modulated at the cellular level through the cell cycle, external signals, and gene expression. CENP-B concentrations serve as crucial regulators of chromosome stability and proper cell division, thereby influencing cell fate. In addition to organizing and distributing chromosomes, CENP-B can also contribute to the onset of diseases, including cancer. By investigating the expression of CENP-B and its role in cell biology and pathophysiology, we can gain insights into its critical importance in AGM cells.
Centromere Protein B Box Localized at Center of Chromosomes
This NH2-terminal DNA-binding domain is essential for human cells, enabling CENP-B to bind to the centromeric regions of human chromosomes in vivo. Consequently, CENP-B's interaction with the CENP-B box may facilitate its localization to the centromeric areas. Additionally, we have demonstrated that AGM CENP-B possesses the same DNA binding domain as human CENP-B and is localized exclusively to the centromeric area of AGM chromosomes. This is particularly evident in the presence of a CENP-B (CENP-B box) recognition sequence within the AGM centromere.
Impact of Centromere Protein B Gene on Mitosis
The centromere protein B gene plays a crucial role in mitotic events, including chromosome alignment, segregation, and cytokinesis. The mechanism of CENP-B overexpression or absence leads to chromosome instability, aneuploidy, and cell cycle dysregulation, highlighting the importance of this protein for maintaining genome stability.
Conclusion
Centromeres, epigenetically coded regions of chromosomes, which are essential for inheritance. CENP-B is a crucial nuclear protein and a transient centromere DNA-binding protein. It primarily associates with chromosome centromeres during cell division and is present in a variety of species. The expression of CENP-B can be regulated by the cell cycle, external signaling, and cellular gene expression. Additionally, CENP-B expression can impact chromosome stability and the precision of cell division, thereby influencing cell fate and function.
References
- Chardon, F.; et al. CENP-B-mediated DNA loops regulate activity and stability of human centromeres. Molecular cell. 2022, 82(9): 1751-1767.
- McKinley, K.; et al. The molecular basis for centromere identity and function. Nature reviews Molecular cell biology. 2016, 17(1): 16-29.
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