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Cohesin is loaded on chromatin in early G1 in vertebrate cells and establishes cohesion during S phase [4], [5].
In budding yeast, the acetyltransferase Eco1/Ctf7 establishes cohesion during DNA replication in S phase and in response to DNA double strand breaks in G2/M phase.
The SMC-1/ 3 "cohesin" complex establishes cohesion between sister chromatids, while the SMC-2/ 4 "condensin" complex mediates chromosome condensation and resolution.
Ctf7 establishes cohesion during S phase, and interacts with components of the DNA replication machinery, including PCNA and RFC [ 5- 7].
Eco1 normally establishes cohesion during DNA replication at S phase, and accumulating evidence indicates the strong connection between cohesion establishment and DNA replication (Skibbens et al. 1999; Kenna and Skibbens 2003; Skibbens 2004; Moldovan et al. 2006).
To understand how cohesin is loaded onto DNA and establishes cohesion, we have generated human cohesin complexes in wild-type (WT), nonacetylatable, and ATP hydrolysis-deficient forms and have analyzed their properties as purified complexes, in Xenopus egg extracts, and by expression in HeLa cells.
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Upon entry into S-phase, as the sister chromatids are being synthesized, the two establishment of cohesion factors, ESCO1 and ESCO2, establish cohesion by securing the cohesin ring around sister chromatids (Skibbens et al., 1999; Hartman et al., 2000; Homer et al., 2005; Skibbens, 2009; Terret et al., 2009).
Both Smc3 acetylation and Scc1 acetylation appeared to counteract the function of Wapl to establish cohesion.
Cohesin-DNA complexes in eco1∆ wpl1∆ cells are stably bound to DNA but fail to establish cohesion, indicating a post-DNA binding step is required for cohesion.
Only 63% mps3 ∆ pom152 ∆ cells established cohesion, which is similar to the amount of cohesion observed in mps3 ∆75–150 mutants (64%) (Ghosh et al. 2012).
Consistent with this idea, cohesin, which established cohesion in S phase, has been reported to be removed genome-wide upon DNA damage in G2/M (McAleenan et al. 2013).
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