Compaction and segregation of sister chromatids via active loop extrusion.

Anton Goloborodko,Maxim V Imakaev,John F Marko,Leonid Mirny

doi:10.7554/elife.14864

Anton Goloborodko, Maxim V Imakaev + Show 2 more

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https://doi.org/10.7554/elife.14864

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Abstract

The mechanism by which chromatids and chromosomes are segregated during mitosis and meiosis is a major puzzle of biology and biophysics. Using polymer simulations of chromosome dynamics, we show that a single mechanism of loop extrusion by condensins can robustly compact, segregate and disentangle chromosomes, arriving at individualized chromatids with morphology observed in vivo. Our model resolves the paradox of topological simplification concomitant with chromosome 'condensation', and explains how enzymes a few nanometers in size are able to control chromosome geometry and topology at micron length scales. We suggest that loop extrusion is a universal mechanism of genome folding that mediates functional interactions during interphase and compacts chromosomes during mitosis.

Highlights

The mechanism whereby eukaryote chromosomes are compacted and concomitantly segregated from one another remains poorly understood
In the second set of simulations, we studied whether loop extrusion and strand passing simultaneously lead to spatial segregation (Nasmyth, 2001) and disentanglement of sister chromatids (Marko, 2009)
Our results show that chromosomal compaction by loop extrusion generates the major features of chromosome reorganization observed during prophase (Nasmyth, 2001; Alipour and Marko, 2012)

Summary

Introduction

The mechanism whereby eukaryote chromosomes are compacted and concomitantly segregated from one another remains poorly understood. A number of aspects of this process are remarkable. The chromosomes are condensed into elongated structures that maintain the linear order, i.e. the order of genomic elements in the elongated chromosome resembles their order along the genome (Trask et al, 1993). The compaction machinery is able to distinguish different chromosomes and chromatids, preferentially forming intra-chromatid cross-links: if this were not the case, segregation would not occur (Nasmyth, 2001). The process of compaction is coincident with segregation of sister chromatids, i.e. formation of two separate chromosomal bodies. Originally intertwined sister chromatids become topologically disentangled, which is surprising, given the general tendency of polymers to become more intertwined as they are concentrated (Marko, 2011)

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