Abstract
SummaryCohesin entraps sister DNAs within tripartite rings created by pairwise interactions between Smc1, Smc3, and Scc1. Because Smc1/3 ATPase heads can also interact with each other, cohesin rings have the potential to form a variety of sub-compartments. Using in vivo cysteine cross-linking, we show that when Smc1 and Smc3 ATPases are engaged in the presence of ATP (E heads), cohesin rings generate a “SMC (S) compartment” between hinge and E heads and a “kleisin (K) compartment” between E heads and their associated kleisin subunit. Upon ATP hydrolysis, cohesin’s heads associate in a different mode, in which their signature motifs and their coiled coils are closely juxtaposed (J heads), creating alternative S and K compartments. We show that K compartments of either E or J type can entrap single DNAs, that acetylation of Smc3 during S phase is associated with J heads, and that sister DNAs are entrapped in J-K compartments.
Highlights
The cohesin complex holds sister chromatids together in post-replicative proliferating cells (Guacci et al, 1997; Michaelis et al, 1997) and organizes the topology of chromatin fibers during interphase (Rao et al, 2017)
It has been suggested that sister chromatid cohesion is mediated by co-entrapment of sister DNAs within a tripartite ring formed by pairwise interactions between cohesin’s Smc1, Smc3, and kleisin (Scc1) subunits (Haering et al, 2002) while chromatid-like structures during interphase are created by a DNA translocase associated with cohesin that progressively extrudes ever-longer loops of DNA (Nasmyth, 2001), an activity thought to be responsible for creating the topologically associated domains (TADs) observed using HiC (Fudenberg et al, 2016; Haarhuis et al, 2017; Rao et al, 2017; Sanborn et al, 2015; Schwarzer et al, 2017; Wutz et al, 2017)
Using Thiol-Specific Cross-Linking to Measure ATPDependent Head Engagement In absence of a crystal structure of Smc1/3 head heterodimers, we identified Smc1 and Smc3 residues predicted to reside within the engaged interface by aligning the structures of homodimeric Smc1 and Smc3 heads from S. cerevisiae, crystalized in the presence of ATP (Figures 1B and 1C) (Gligoris et al, 2014; Haering et al, 2004)
Summary
The cohesin complex holds sister chromatids together in post-replicative proliferating cells (Guacci et al, 1997; Michaelis et al, 1997) and organizes the topology of chromatin fibers during interphase (Rao et al, 2017) The former involves interactions between different DNA molecules that must be stable for very extended periods of time, possibly years in the case of meiotic cells (Hunt and Hassold, 2010), while the latter involves transient long-range interactions between sequences from the same DNA molecule that organize chromosomal DNAs into chromatid-like threads with loops emanating from a central axis (Klein et al, 1999; Tedeschi et al, 2013). Additional interactions between Smc and Smc in the vicinity of their ATPase heads may divide the large ring created by joining Smc hinge and Smc/kleisin interfaces into two sub-compartments as described in the present study, namely a ‘‘SMC (S) compartment’’ created by the Smc1/3 hinge and Smc1/3 head interactions and a ‘‘kleisin (K) compartment’’ defined by Smc1/3 head interactions and interactions of each ATPase head with the N- and C-terminal domains of Scc
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