Association of condensin with chromosomes depends on DNA binding by its HEAT-repeat subunits

Abstract

Condensin complexes have central roles in the three-dimensional organization of chromosomes during cell divisions, but how they interact with chromatin to promote chromosome segregation is largely unknown. Previous work has suggested that condensin, in addition to encircling chromatin fibers topologically within the ring-shaped structure formed by its SMC and kleisin subunits, contacts DNA directly. Here we describe the discovery of a binding domain for double-stranded DNA formed by the two HEAT-repeat subunits of the Saccharomyces cerevisiae condensin complex. From detailed mapping data of the interfaces between the HEAT-repeat and kleisin subunits, we generated condensin complexes that lack one of the HEAT-repeat subunits and consequently fail to associate with chromosomes in yeast and human cells. The finding that DNA binding by condensin's HEAT-repeat subunits stimulates the SMC ATPase activity suggests a multistep mechanism for the loading of condensin onto chromosomes.

HEAT repeats – versatile arrays of amphiphilic helices working in crowded environments?

“…It should also be added that, like in NPCs, HEAT repeats and IDRs could also functionally cooperate in mitotic chromosome assembly. For instance, the HEAT subunits of condensins interact with conserved hydrophobic patches present in the central IDR of the kleisin subunits (Piazza et al, 2014). The HEAT subunits themselves also contain IDRs.…”

RotoStep: A Chromosome Dynamics Simulator Reveals Mechanisms of Loop Extrusion

“…The SMC protein coiled-coils are represented by beads 2-8. To achieve DNA binding, we assert that the heat-repeat proteins (Ycs4, Ycg1) bind DNA (Piazza et al 2014). These are beads 1 (representing Ycg1, red in Fig.…”

Condensin II mutation causes T-cell lymphoma through tissue-specific genome instability

“…Evidence supporting this hypothesis recently arose from a gene network-based analysis of The Cancer Genome Atlas (TCGA) data set (Leiserson et al 2015). With the exception of SMC4, mutations in condensin subunits were not statistically enriched in tumor genomes when considered individually; however, statistical significance was reached when subunits were considered together as a (Bürmann et al 2013;Piazza et al 2014). The box indicates the region that is expanded in B.…”

“…In eukaryotes, each SMC complex contains a heterodimer of SMC ATPase subunits, a single kleisin subunit, and additional accessory factors (Fig 1A;Losada and Hirano 2005;Nasmyth and Haering 2005). Within cohesin and condensin complexes, the C and N termini of kleisin interact with apposing SMC subunits to form a tripartite, asymmetric ring-like structure that can entrap DNA (Gruber et al 2003;Onn et al 2007; Nasmyth and Oliveira 2010; Cuylen et al 2011;Piazza et al 2014). This mode of association has been proposed to allow SMC complexes to form topological linkages between chromosomes or different regions on the same DNA molecule.…”