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Dynamics of sister chromatid resolution during cell cycle progression

By Rugile Stanyte, Johannes Nuebler, Claudia Blaukopf, Rudolf Hoefler, Roman Stocsits, Jan-Michael Peters, Daniel W. Gerlich

Posted 16 Mar 2018
bioRxiv DOI: 10.1101/283770 (published DOI: 10.1083/jcb.201801157)

Faithful genome transmission in dividing cells requires that the two copies of each chromosome's DNA package into separate, but physically linked, sister chromatids. The linkage between sister chromatids is mediated by cohesin, yet where sister chromatids are linked and how they resolve during cell cycle progression has remained unclear. Here, we investigated sister chromatid organization in live human cells using dCas9-mEGFP labelling of endogenous genomic loci. We detected substantial sister locus separation during G2 phase, irrespective of the proximity to cohesin enrichment sites. Almost all sister loci separated within a few hours after their respective replication, and then rapidly equilibrated their average distances within dynamic chromatin polymers. Our findings explain why the topology of sister chromatid resolution in G2 largely reflects the DNA replication program. Further, these data suggest that cohesin enrichment sites are not persistent cohesive sites in human cells. Rather, cohesion might occur at variable genomic positions within the cell population.

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