Mitosis, the process of cell division, requires the precise distribution of genetic material to two new daughter cells. Before division, the cell must duplicate its entire set of chromosomes during the S phase of the cell cycle. This replication results in two identical copies of each chromosome, which are temporarily held together.
These identical copies, referred to as sister chromatids, must remain physically connected until the final stage of alignment. This physical linkage ensures that the two copies attach to spindle fibers from opposite sides of the cell. This connection guarantees that each daughter cell receives exactly one complete set of chromosomes, preventing errors in genetic inheritance.
The Cohesin Complex
The protein assembly responsible for this physical linkage is the cohesin complex. This complex acts as a molecular “glue” that binds the replicated DNA molecules together following synthesis. Cohesin’s structure involves four core subunits, including two large Structural Maintenance of Chromosomes (SMC) proteins: SMC1 and SMC3.
The two SMC proteins form a V-shaped dimer connected by a hinge domain, which is closed by two non-SMC regulatory subunits. One regulatory subunit, often called Scc1 or Rad21 in humans, acts as a “kleisin” that links the two SMC protein heads. The complex is loaded onto the DNA during the S phase and remains tightly associated with the chromatids throughout the subsequent phases of the cell cycle.
The Molecular Mechanism of Cohesion
The cohesin complex maintains the physical connection between sister chromatids through a mechanism of topological entrapment. The four subunits assemble to form a large, closed ring structure. This molecular ring physically encircles both sister chromatids, holding them together like a handcuff around a pair of wrists.
The chromatids are linked not by a chemical bond between the DNA strands, but by physical enclosure within the protein ring. Cohesin rings are distributed along the chromosomes but are concentrated in the centromere region. This concentration helps maintain the connection against the pulling forces of the spindle fibers during the alignment phase.
Regulating the Separation
The bond created by the cohesin complex must be broken at a precise moment to allow the sister chromatids to separate and move to opposite poles. This separation is controlled to occur only at the transition from metaphase to anaphase, marking the end of the alignment process. The enzyme responsible for dissolving this connection is a specific protease called Separase.
Separase is activated only after the cell confirms that all chromosomes are correctly aligned on the spindle. Separase targets and cleaves the Scc1 subunit of the cohesin ring. Cutting this subunit opens the molecular ring, causing the cohesin complex to dissociate from the chromosomes. The release of the physical constraint allows the sister chromatids to be pulled apart by the spindle apparatus, completing the segregation of the genetic material.