Abstract
The cohesin complex facilitates faithful chromosome segregation by pairing the sister chromatids after DNA replication until mitosis. In addition, cohesin contributes to proficient and error-free DNA replication. Replisome progression and establishment of sister chromatid cohesion are intimately intertwined processes. Here, we review how the key factors in DNA replication and cohesion establishment cooperate in unperturbed conditions and during DNA replication stress. We discuss the detailed molecular mechanisms of cohesin recruitment and the entrapment of replicated sister chromatids at the replisome, the subsequent stabilization of sister chromatid cohesion via SMC3 acetylation, as well as the role and regulation of cohesin in the response to DNA replication stress.
Highlights
Every cell division requires the duplication and separation of the entire genome to ensure that each daughter cell receives a complete copy
Cohesin rings are removed in two steps: A phosphorylation-dependent process triggers WAPL-mediated cohesin release from chromosome arms during prophase, followed by protease-dependent cleavage of remaining rings at centromeres at anaphase onset, which triggers the separation of sister chromatids to opposite sides of the cell [1]
We describe how the cohesin complex is recruited to the replisome, how many replisome factors play dual roles in cohesion establishment and DNA replication and to what extent these processes can be separated, as well as the role of cohesin and cohesion-associated factors in the response to DNA replication stress
Summary
Every cell division requires the duplication and separation of the entire genome to ensure that each daughter cell receives a complete copy. A critical step for faithful chromosome segregation is the stable cohesion between replicated sister chromatids, mediated by the cohesin complex and established at the DNA replication fork. The cohesin complex consists of two coiled-coil subunits, SMC1A and SMC3, the kleisin subunit RAD21, and the additional subunits STAG1/2 and PDS5A/B. Together, these components form a ringshaped structure, which can engage DNA in topological and non-topological manners and is essential for proliferation [1,2]. Before DNA replication, the association of cohesin with chromatin is dynamic due to the release activity of WAPL [13,14].
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