What are Sister Chromatids?
Sister chromatids are two identical copies of a single replicated chromosome that are connected by a common centromere. They are formed during the S phase of the cell cycle, where a chromosome is duplicated to ensure that each daughter cell receives an identical set of chromosomes during cell division.
Role of Cohesion in Chromatid Pairing
The cohesion of sister chromatids is a crucial aspect of chromosomal behavior during cell division. This cohesion is primarily mediated by a protein complex known as cohesin. Cohesin rings encircle the sister chromatids, holding them together from the time of their replication in S phase until their separation during anaphase. This cohesion is essential for the accurate segregation of chromosomes, preventing aneuploidy, which can lead to various diseases, including cancer.Structure and Function of Cohesin Complex
The cohesin complex is composed of several core subunits, including SMC1, SMC3, RAD21, and SCC3. These proteins form a ring-like structure that physically encircles the sister chromatids. Cohesin not only maintains cohesion but also plays a role in DNA repair, chromatin organization, and gene expression. The proper functioning of cohesin is regulated by numerous factors, including post-translational modifications and interactions with other proteins.Mechanism of Cohesion Establishment and Maintenance
Cohesion between sister chromatids is established during DNA replication. The cohesin complex is loaded onto chromosomes during G1 phase and becomes cohesive when the DNA is replicated. The establishment of cohesion involves the acetylation of SMC3 by the acetyltransferase ESCO1/2, which stabilizes cohesin on the chromatin. Maintenance of cohesion until anaphase is crucial and is controlled by proteins such as sororin, which inhibit the cohesin-destabilizing activity of WAPL.Separation of Sister Chromatids
The separation of sister chromatids occurs during anaphase of mitosis and meiosis II. This process is tightly regulated by the anaphase-promoting complex/cyclosome (APC/C), which targets securin for degradation. Securin inhibits separase, a protease that cleaves the cohesin complex. Once securin is degraded, separase becomes active and cleaves the RAD21 subunit of cohesin, leading to the release of sister chromatids. This separation allows for the equal distribution of chromosomes to the daughter cells.Importance in Histology and Medical Implications
In histology, understanding the cohesion of sister chromatids is vital for interpreting cell division and identifying abnormalities. Errors in cohesion can lead to chromosomal instability, a hallmark of many cancers. Defects in cohesion are also associated with several genetic disorders, such as Cornelia de Lange syndrome and Roberts syndrome, which are characterized by developmental abnormalities and growth defects.Conclusion
The cohesion of sister chromatids is an essential process for accurate chromosome segregation during cell division. It involves a complex interplay of proteins that ensure the proper pairing and eventual separation of chromatids. Understanding this process is crucial in histology for diagnosing and studying various diseases related to chromosomal abnormalities.
