Establishment of sister chromatid cohesion
In general, cohesion is established during S phase as DNA is replicated, and is lost when chromosomes segregate during mitosis and meiosis.
Cohesin must undergo subsequent modification ("establishment") to be capable of physically holding the sister chromosomes together.
[4] Though cohesin can associate with chromatin earlier in the cell cycle, cohesion is established during S phase.
Tying establishment to DNA replication allows the cell to institute cohesion as soon as the sister chromatids are formed.
At entry to mitosis, Sororin is phosphorylated and replaced again by Wapl, leading to loss of cohesion.
A similar function-specific alternative RFC (replacing RFC1 with Rad24) plays a role in the DNA damage checkpoint.
[14] Though the protein was originally identified as a Topoisomerase I redundant factor, the TRF4 gene product was later shown to be required for sister chromatid cohesion.
In the same paper in which they identified Pol σ, Wang et al. suggested a polymerase switch model for establishment of cohesion.
[17] In this model, upon reaching a CAR, the cell switches DNA polymerases in a mechanism similar to that used in Okazaki fragment synthesis.
The cell off-loads the processive replication polymerase and instead uses Pol σ for synthesis of the CAR region.
Thus, it is possible that cohesion is required for this process because it ensures that the sister chromatids are physically close enough to undergo HR.
In the presence of ionizing radiation (IR), the Smc1 subunit of cohesin is phosphorylated by the ataxia telangiectasia mutated (ATM) kinase.
In the bacterium Escherichia coli, repair of mitomycin C-induced DNA damages occurs by a sister chromatid cohesion process involving the RecN protein.
[20] Sister chromatid interaction followed by homologous recombination appears to significantly contribute to the repair of DNA double-strand damages.
Defects in the establishment of sister chromatid cohesion have serious consequences for the cell and are therefore tied to many human diseases.
The loss of the human homologs of core cohesin proteins or of Eco1, Pds5, Wapl, Sororin, or Scc2 has been tied to cancer.
Diseases arising from defects in cohesin or other proteins involved in sister chromatid cohesion are referred to as cohesinopathies.
