Evolution of condensin and cohesin complexes driven by replacement of Kite by Hawk proteins

Abstract

SummaryMitotic chromosome condensation, sister chromatid cohesion, and higher order folding of interphase chromatin are mediated by condensin and cohesin, eukaryotic members of the SMC (structural maintenance of chromosomes)–kleisin protein family. Other members facilitate chromosome segregation in bacteria [1]. A hallmark of these complexes is the binding of the two ends of a kleisin subunit to the apices of V-shaped Smc dimers, creating a tripartite ring capable of entrapping DNA (Figure 1A). In addition to creating rings, kleisins recruit regulatory subunits. One family of regulators, namely Kite dimers (Kleisin interacting winged-helix tandem elements), interact with Smc–kleisin rings from bacteria, archaea and the eukaryotic Smc5-6 complex, but not with either condensin or cohesin [2]. These instead possess proteins containing HEAT (Huntingtin/EF3/PP2A/Tor1) repeat domains whose origin and distribution have not yet been characterized. Using a combination of profile Hidden Markov Model (HMM)-based homology searches, network analysis and structural alignments, we identify a common origin for these regulators, for which we propose the name Hawks, i.e. HEAT proteins associated with kleisins.

The biology and polymer physics underlying large‐scale chromosome organization

“…Whether cohesin binds as a single complex or 2 linked complexes and the mechanism by which cohesin associates with and then dissociates from DNA are also unknown . (d) SMC protein complexes in eukaryotes (cohesin, condensin, SMC5/6) and prokaryotes are tripartite ring‐shaped ATPases, composed of 2 SMC proteins, (light blue, dark blue), and a Kleisin linker protein (green) that joins their head domains and assembles the nucleotide binding domain, and to which one of a family of HEAT protein regulators (yellow) bind . Although they share a common architecture, these complexes vary in composition (SMCs are heterodimers in eukaryotes but homodimers in prokaryotes) and biological function, which may be influenced by the Kleisin subunit and/or the Kleisin‐associated HEAT‐family regulatory component…”

“…Cohesin was discovered and is best characterized in the budding yeast S. cerevisiae , for its role in holding sister chromatids together during mitosis until they are properly aligned and captured by the mitotic spindle and only then releasing them to allow for their segregation, Figure B. This function of cohesin may have evolved more recently than its role in loop formation …”

“…Given these caveats, we will use specific examples to address questions about the evolution and evolutionary conservation of the proteins that shape and organize genomes and the mechanisms by which they carry out these functions. For comprehensive reviews, readers are referred to several informative articles …”

DNA entry, exit and second DNA capture by cohesin: insights from biochemical experiments

“…In addition, Scc1 interacts with the HEAT repeat Scc3 subunit which regulates chromatin association of cohesin. Using its flexible middle domain, Scc1 also serves as a docking platform for the HEAT repeat auxiliary proteins Pds5 and Scc2 [26–29]. Scc2, with its stable binding partner Scc4, promotes cohesin loading [30] whereas Pds5, with its substoichiometric binding partner Wapl, dissociates cohesin from chromatin [31–33].…”

“…These results suggest that Wapl initially destabilizes the Smc3-Scc1 interaction and Pds5 then keeps the DNA transport gate open. Crystallographic and bioinformatic studies have shown that Pds5 and Scc2, as well as Scc3, are paralogs and share similar U-shaped structures that are composed of stacked HEAT repeat helices [27–29,40]. Both Pds5 and Scc2 interact with the flexible middle domain of Scc1.…”