Cohesin

Cohesin is a protein complex that regulates the segregation of chromosomes during cell division (both mitosis and meiosis). It plays a critical role in chromosome structure and function, ensuring that sister chromatids are properly aligned and separated. Cohesin is also involved in DNA repair, gene expression, and the maintenance of genome stability.

Structure and Function

Cohesin is composed of several core subunits: SMC1 (Structural Maintenance of Chromosomes 1), SMC3, RAD21 (also known as SCC1), and either SA1 or SA2 (Stromal Antigen 1/2). These proteins form a ring-like structure that encircles DNA, holding sister chromatids together from the time of their replication in S phase until their separation during anaphase of cell division.

Chromosome Cohesion

The primary function of cohesin is to mediate the cohesion of sister chromatids. This process begins in S phase, where cohesin complexes are loaded onto chromosomes by the loading complex, consisting of SCC2 and SCC4. Cohesion is then established during DNA replication, ensuring that each sister chromatid is identical and properly aligned for separation.

Regulation of Cohesin

The regulation of cohesin's association with chromosomes is tightly controlled by various proteins and processes. For instance, the protein kinase CDK1 phosphorylates cohesin, which is thought to regulate its association with chromosomes. Additionally, the protein WAPL promotes the removal of cohesin from chromosomes, a process that is essential for proper chromosome segregation during anaphase.

Role in DNA Repair

Cohesin also plays a significant role in the repair of DNA double-strand breaks through the process of homologous recombination. By holding sister chromatids together, cohesin ensures that there is a template available for error-free DNA repair, thus maintaining genomic stability.

Genetic Disorders

Mutations in the genes encoding cohesin subunits or its regulators can lead to a variety of developmental disorders, collectively known as "cohesinopathies." These include Cornelia de Lange Syndrome (CdLS) and Roberts Syndrome, which are characterized by growth retardation, limb and organ abnormalities, and intellectual disability. The molecular basis of these disorders involves disruptions in the normal function of cohesin, affecting chromosome segregation, DNA repair, and gene expression.

Research and Clinical Implications

Understanding the complex roles of cohesin in cell division, DNA repair, and gene expression has significant implications for cancer research and the development of therapeutic strategies. Aberrations in cohesin function are associated with chromosomal instability, a hallmark of cancer cells. Targeting the pathways that regulate cohesin and its interaction with chromosomes may offer new avenues for cancer therapy.