PT  - JOURNAL ARTICLE
AU  - Paul Batty
AU  - Christoph C.H. Langer
AU  - Zsuzsanna Takács
AU  - Wen Tang
AU  - Claudia Blaukopf
AU  - Jan-Michael Peters
AU  - Daniel W. Gerlich
TI  - Cohesin-mediated DNA loop extrusion resolves sister chromatids in G2 phase
AID  - 10.1101/2023.01.12.523718
DP  - 2023 Jan 01
TA  - bioRxiv
PG  - 2023.01.12.523718
4099  - http://biorxiv.org/content/early/2023/01/12/2023.01.12.523718.short
4100  - http://biorxiv.org/content/early/2023/01/12/2023.01.12.523718.full
AB  - Genetic information is stored in linear DNA molecules, which fold extensively inside cells. DNA replication along the folded template path yields two sister chromatids that initially occupy the same nuclear region in a highly intertwined arrangement. Dividing cells must disentangle and condense the sister chromatids into separate bodies such that a microtubule-based spindle can move them to opposite poles. While the spindle-mediated transport of sister chromatids has been studied in detail, the chromosome-intrinsic mechanics pre-segregating sister chromatids have remained elusive. Here, we show that human sister chromatids resolve extensively already during interphase, in a process dependent on the loop-extruding activity of cohesin, but not that of condensins. Increasing cohesin’s looping capability increases sister DNA resolution in interphase nuclei to an extent normally seen only during mitosis, despite the presence of abundant arm cohesion. That cohesin can resolve sister chromatids so extensively in the absence of mitosis-specific activities indicates that DNA loop extrusion is a generic mechanism for segregating replicated genomes, shared across different Structural Maintenance of Chromosomes (SMC) protein complexes in all kingdoms of life.Competing Interest StatementThe authors have declared no competing interest.