Genome folding through loop extrusion by SMC complexes

Cryo-EM structure of MukBEF reveals DNA loop entrapment at chromosomal unloading sites

“…Associations between molecules due to their topology are known as mechanical bonds (Stoddart, 2009). In eukaryotes as well as prokaryotes, ring-like SMC complexes are thought to structure chromosomes via mechanical bonds with DNA (also referred to as 'DNA entrapment'), and active DNA loop extrusion (Davidson and Peters, 2021;Hassler et al, 2018;Mäkelä and Sherratt, 2020a;Nasmyth, 2001;Yatskevich et al, 2019). These activities have been suggested to enable or facilitate processes such as lengthwise condensation of chromosomes, sister chromatid cohesion, regulation of interactions between enhancers and distant promoters, disentangling of replicated DNA by topoisomerases, DNA recombination, and DNA double-strand break repair.…”

SMC complexes can traverse physical roadblocks bigger than their ring size

“…Early molecular models for loop extrusion suggested that the SMC ring topologically embraces the DNA upon loading and during DNA loop extrusion. 31,40 More recently, also a pseudotopological 11,41,13 and nontopological loading 13,42 of the DNA were considered. The data from the current study provide unambiguous evidence for a nontopological mode for DNA loop extrusion, where DNA must bind externally to the SMC complex.…”

The loopy world of cohesin

“…A protein complex thought to be involved in these arrangements is a ring-like structure called cohesin ( Figure 1A ). It performs two main roles: firstly, it provides ‘cohesion’ between replicated chromatin by holding sister chromatids together during cell division until the cell is ready to segregate them into two daughter cells ( Nasmyth and Haering, 2005 ; Davidson and Peters, 2021 ). Secondly, it makes chromatin loops that build functional domains, limitingcurbing chromatin motion ( Nozaki et al, 2017 ; Davidson and Peters, 2021 ).…”

“…A recent model, called loop extrusion, suggests that genomic DNA is constantly pushed out through the cohesin ring to form loops ( Davidson and Peters, 2021 ). This mechanism is thought to keep local regions of DNA together while disentangling them from other parts of the genome.…”

“…Cohesin contains two subunits called Smc1 and Smc3 that each contain a hinge domain that joins the two molecules together ( Figure 1A ; Davidson and Peters, 2021 ). At the other end of each subunit is an ATPase head which can bind and hydrolyze ATP: this causes the ATPase head to join together or disassociate from one another depending on the situation.…”