Abstract
SummaryCohesin organizes DNA into chromatids, regulates enhancer-promoter interactions, and confers sister chromatid cohesion. Its association with chromosomes is regulated by hook-shaped HEAT repeat proteins that bind Scc1, namely Scc3, Pds5, and Scc2. Unlike Pds5, Scc2 is not a stable cohesin constituent but, as shown here, transiently replaces Pds5. Scc1 mutations that compromise its interaction with Scc2 adversely affect cohesin’s ATPase activity and loading. Moreover, Scc2 mutations that alter how the ATPase responds to DNA abolish loading despite cohesin’s initial association with loading sites. Lastly, Scc2 mutations that permit loading in the absence of Scc4 increase Scc2’s association with chromosomal cohesin and reduce that of Pds5. We suggest that cohesin switches between two states: one with Pds5 bound that is unable to hydrolyze ATP efficiently but is capable of release from chromosomes and another in which Scc2 replaces Pds5 and stimulates ATP hydrolysis necessary for loading and translocation from loading sites.
Highlights
How enhancers activate the correct promoters during development, how chromosomal DNAs are woven into chromatids, and how sisters are held together during mitosis are all fundamental questions in chromosome biology
All three are monophyletic with equivalent subunits in condensin. This class of regulatory subunit called HAWKs (HEAT repeat proteins associated with kleisins) distinguishes cohesin and condensin (Wells et al, 2017) from bacterial Smc/ kleisin complexes and the eukaryotic Smc5/6 complex, whose kleisin subunits associate instead with tandem winged helical domain proteins called Kleisin interacting winged-helix tandem elements (KITEs) (Palecek and Gruber, 2015)
Little or no ATPase activity was associated with any of these, even in the presence of DNA
Summary
How enhancers activate the correct promoters during development, how chromosomal DNAs are woven into chromatids, and how sisters are held together during mitosis are all fundamental questions in chromosome biology. These apparently disparate processes are conferred by a pair of related Smc/ kleisin complexes called cohesin and condensin. Both contain a pair of rod-shaped Smc proteins that associate to create V-shape heterodimers (Smc1/3 in cohesin), whose ATPases at their apices are bound by the N- and C-terminal domains of a kleisin subunit (Scc1), forming a huge tripartite ring. This class of regulatory subunit called HAWKs (HEAT repeat proteins associated with kleisins) distinguishes cohesin and condensin (Wells et al, 2017) from bacterial Smc/ kleisin complexes and the eukaryotic Smc5/6 complex, whose kleisin subunits associate instead with tandem winged helical domain proteins called Kleisin interacting winged-helix tandem elements (KITEs) (Palecek and Gruber, 2015)
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