What Attaches Sister Chromatids to Each Other?

Sister chromatids are the duplicated form of a chromosome, consisting of two identical DNA copies joined together. This pairing is a direct result of DNA replication, a process where a cell duplicates its genetic material before dividing. Each sister chromatid contains identical genetic information, ensuring that when the cell divides, daughter cells receive a complete and accurate set of chromosomes. The temporary attachment between these identical copies is a fundamental step, preparing the cell for proper distribution of genetic material during cell division.

The Molecular Glue Holding Them Together

The attachment of sister chromatids is managed by a specialized protein complex known as cohesin. This complex acts as a molecular “glue,” encircling the two DNA molecules to hold them in close proximity. Cohesin forms a ring-like structure that entraps the sister chromatids, preventing premature separation.

The cohesin complex is composed of four core subunits: Smc1, Smc3, Scc1 (also called Rad21), and Scc3 (known as SA1 or SA2). Smc1 and Smc3 are part of the Structural Maintenance of Chromosomes (SMC) family, characterized by long, coiled-coil arms that connect an ATP-binding “head” domain and a hinge domain. These two SMC proteins dimerize through their hinge domains, forming a V-shaped structure. The Scc1 subunit bridges the head domains of Smc1 and Smc3, completing the closed ring structure that encircles the DNA. The Scc3 subunit associates with Scc1, stabilizing the complex. This arrangement ensures robust physical linkage between the sister chromatids along their lengths.

Why This Attachment Matters for Cell Division

The cohesion between sister chromatids is essential for accurate chromosome segregation during cell division, encompassing both mitosis and meiosis. This attachment ensures that when chromosomes align in the center of the cell, each sister chromatid is properly oriented towards opposite poles of the dividing cell. Spindle fibers attach to the centromere, pulling on the attached sister chromatids.

Maintaining this attachment is important for balancing the pulling forces from the opposing spindle poles, which is necessary for the proper function of the mitotic spindle checkpoint. This checkpoint monitors chromosome alignment to ensure that each daughter cell receives a full complement of chromosomes. Without proper cohesion, chromosomes could be unevenly distributed, leading to genetic abnormalities such as aneuploidy (an abnormal number of chromosomes). This regulation also aids DNA repair, as the intact sister chromatid can serve as a template for repairing damage on its counterpart.

When and How They Separate

The separation of sister chromatids is a highly regulated event that occurs primarily during anaphase of cell division. This separation is initiated by the controlled breakdown of the cohesin complex. The enzyme responsible for this action is separase, a cysteine protease.

Separase becomes active at the onset of anaphase and cleaves the Scc1 (Rad21) subunit of the cohesin ring. This cleavage breaks open the cohesin ring, releasing the physical link between the sister chromatids. Once released, the sister chromatids are pulled apart by the spindle fibers to opposite ends of the cell, becoming individual chromosomes. This timely and irreversible process is tightly controlled to ensure accurate chromosome segregation, preventing errors that could lead to cellular dysfunction.