Condensins and cohesins - one of these things is not like the other!

Robert V Skibbens

doi:10.1242/jcs.220491

Abstract

Condensins and cohesins are highly conserved complexes that tether together DNA loci within a single DNA molecule to produce DNA loops. Condensin and cohesin structures, however, are different, and the DNA loops produced by each underlie distinct cell processes. Condensin rods compact chromosomes during mitosis, with condensin I and II complexes producing spatially defined and nested looping in metazoan cells. Structurally adaptive cohesin rings produce loops, which organize the genome during interphase. Cohesin-mediated loops, termed topologically associating domains or TADs, antagonize the formation of epigenetically defined but untethered DNA volumes, termed compartments. While condensin complexes formed through cis-interactions must maintain chromatin compaction throughout mitosis, cohesins remain highly dynamic during interphase to allow for transcription-mediated responses to external cues and the execution of developmental programs. Here, I review differences in condensin and cohesin structures, and highlight recent advances regarding the intramolecular or cis-based tetherings through which condensins compact DNA during mitosis and cohesins organize the genome during interphase.

Highlights

The genome of a cell undergoes a myriad of complex structural contortions
These findings argue that a separate structural maintenance of chromosome (SMC)/condensin complex binds to and translocates along each side of the ParS– ParB deposition site, and that the flanking DNA sequences are tethered together through condensin oligomerizations – akin to that posited for cohesins
Pds5 was first identified as supporting cohesin roles in both trans- and cis-tethering, Pds5 binds to the cohesin release factor WAPL and this association is highly conserved (Hartman et al, 2000; Panizza et al, 2000; Losada et al, 2005; Sutani et al, 2009; Shintomi and Hirano, 2009; Ouyang et al, 2016; Goto et al, 2017). These results suggest that Pds5 stabilizes cohesin tethers but can promote cohesin release in coordination with WAPL. Does this premature condensation during interphase involve condensins? Importantly, depletion of the condensin component Smc2 does not block vermicelli formation in cells co-depleted of WAPL and PDS5 (Wutz et al, 2017), indicating that chromatin compaction during interphase is mediated by cohesins

Summary

Introduction

The genome of a cell undergoes a myriad of complex structural contortions. For instance, the products of chromosome duplication, termed sister chromatids, become tethered together during S phase in a process that is coupled to DNA replication (reviewed in Skibbens, 2008; Villa-Hernández and Bermejo, 2018). In the absence of imposed architecture (nucleosomes, chromatin remodelers, SMC complexes, etc.), condensin could bind any proximal segment of a floppy, wriggling DNA and in a non-directed fashion (Fudenberg et al, 2016; Lawrimore et al, 2016, 2017) This model, does not lend itself to explain unidirectional motion or accommodate the tension that is likely generated on DNA during condensation. Migration was greatly decreased in the direction that contained the operon, but not in the direction that was free of active transcription (Wang et al, 2017) These findings argue that a separate SMC/condensin complex binds to and translocates along each side of the ParS– ParB deposition site, and that the flanking DNA sequences are tethered together through condensin oligomerizations – akin to that posited for cohesins (reviewed in Skibbens, 2008; Onn et al, 2008; Zhang et al, 2008). Given the range of tissues impacted by cohesin mutation, and the genome-wide effect that cohesins exert on gene transcription (see below), one should anticipate that the number of cohesin-related maladies or cohesinopathies (more recently termed transcriptomopathies and which include ribosomopathies) will increase significantly over time (Wendt et al, 2008; Xu et al, 2014; Yuan et al, 2015; Skibbens et al, 2013; Banerji et al, 2017a)

C Gene-specified effects

Conclusions and perspectives