A folded conformation of MukBEF and cohesin

Bürmann, Frank; Lee, Byung-Gil; Than, Thane; Sinn, Ludwig; O’Reilly, Francis J.; Yatskevich, Stanislau; Rappsilber, Juri; Hu, Bin; Nasmyth, K; Löwe, Jan

doi:10.1038/s41594-019-0196-z

Cited by 132 publications

(160 citation statements)

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“…The ATP binding induces changes in the mutual positions (and conformations) of the SMC heads and arms 10,27,[46][47][48] . Consequently, the shape of the whole SMC complex changes from a rod-like conformation (with juxtaposed arms stabilized by their mutual interactions) to the less stable open ring (Fig.…”

Section: Discussionmentioning

confidence: 99%

A role of the Nse4 kleisin and Nse1/Nse3 KITE subunits in the ATPase cycle of SMC5/6

Vondrová

Kolesar

Adamus

et al. 2020

Sci Rep

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The SMC (Structural Maintenance of Chromosomes) complexes are composed of SMC dimers, kleisin and kleisin-interacting (HAWK or KITE) subunits. Mutual interactions of these subunits constitute the basal architecture of the SMC complexes. In addition, binding of ATP molecules to the SMC subunits and their hydrolysis drive dynamics of these complexes. Here, we developed new systems to follow the interactions between SMC5/6 subunits and the relative stability of the complex. First, we show that the N-terminal domain of the Nse4 kleisin molecule binds to the SMC6 neck and bridges it to the SMC5 head. Second, binding of the Nse1 and Nse3 KITE proteins to the Nse4 linker increased stability of the ATP-free SMC5/6 complex. In contrast, binding of ATP to SMC5/6 containing KITE subunits significantly decreased its stability. Elongation of the Nse4 linker partially suppressed instability of the ATP-bound complex, suggesting that the binding of the KITE proteins to the Nse4 linker constrains its limited size. Our data suggest that the KITE proteins may shape the Nse4 linker to fit the ATP-free complex optimally and to facilitate opening of the complex upon ATP binding. This mechanism suggests an important role of the KITE subunits in the dynamics of the SMC5/6 complexes.

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Section: Discussionmentioning

confidence: 99%

A role of the Nse4 kleisin and Nse1/Nse3 KITE subunits in the ATPase cycle of SMC5/6

Vondrová

Kolesar

Adamus

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…The ATP binding induces changes in the mutual positions (and conformations) of the SMC heads and arms [10, 26, 46–48]. Consequently, the shape of the whole SMC complex changes from a rod-like conformation (with juxtaposed arms stabilized by their mutual interactions) to the less stable open ring (Fig.…”

Section: Discussionmentioning

confidence: 99%

A role of the Nse4 kleisin and Nse1/Nse3 KITE subunits in the ATPase cycle of SMC5/6

Vondrová

Adamus

Nociar

et al. 2019

Preprint

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1 0 1 1 Keywords: SMC5/6 complex; Nse4 klesin linker; Nse1/Nse3 KITE subunits; ATP binding; 1 2 protein-protein interaction, fission yeast 1 3 1 4 2 ABSTRACT 1 5 The SMC (Structural Maintenance of Chromosomes) complexes are composed of 1 6 SMC dimers, kleisin and kleisin-interacting subunits. Mutual interactions of these subunits 1 7 constitute the basal architecture of the SMC complexes. Particularly, terminal domains of the 1 8 kleisin subunit bridge the SMC head domains of the SMC molecules. Binding of ATP 1 9molecules to the heads and their hydrolysis alter the shape of long SMC molecules (from rod-2 0 3 1 upon ATP binding. This mechanism suggests an important role of the KITE subunits in the 3 2 dynamics of the SMC5/6 complexes. 3 3 3 4 AUTHOR SUMMARY 3 5The SMC5/6 complex is member of the Structural maintenance of chromosomes 3 6 (SMC) family, key organizers of both prokaryotic and eukaryotic genomes. Their architecture 3 7 and dynamics (driven by ATP binding and hydrolysis) are essential for cellular processes, like 3 8 3 chromatin segregation, condensation, replication and repair. In this paper, we described 3 9 conserved mode of the Nse4 kleisin subunit binding to the SMC6 (similar to cohesin and 4 0 condensin) and its bridging role. Furthermore, we showed different impact of the binding of 4 1 the Nse1-Nse3 KITE subunits to the Nse4 kleisin bridge. Our study suggested that the KITE 4 2 proteins modulate the stability of the SMC5/6 complex, depending on its binding and 4 3 hydrolysis of ATP. Our findings uncover molecular mechanisms underlying dynamics of the 4 4 SMC5/6 complexes.4 5 4 6 INTRODUCTION 4 7 The SMC (Structural Maintenance of Chromosomes) complexes are key organizers of 4 8 prokaryotic and eukaryotic genomes. They organize chromatin domains (cohesins; [1]), 4 9 condense mitotic chromosomes (condensins; [2]), assist in DNA repair (SMC5/6; [3, 4]) and 5 0 replication (SMC/ScpAB; [5]). These circular complexes use the energy of ATP hydrolysis to 5 1 drive DNA topology changes. In prokaryotes, SMC/ScpAB drives extrusion of loops forming 5 2 behind the replication fork. In eukaryotes, condensins extrude loops laterally and axially to 5 3 shape chromatin to the typical mitotic chromosomes. Cohesins assist in formation of 5 4 topologically associating domains during interphase. Cohesin rings can also hold newly 5 5 replicated sister chromatids together and release them in highly controlled manner. The 5 6 SMC5/6 complexes have been implicated in the repair of DNA damage by homologous 5 7 recombination, stabilization and restart of stressed replication forks. The SMC5/6 instability 5 8 leads to the chromosome breakage syndrome in human [6], however, the molecular 5 9mechanism of the SMC5/6 action is largely unclear. 6 0 All the SMC complexes are composed of three common categories of subunits: SMC, 6 1 kleisin and kleisin-interacting proteins [7, 8]. The SMC proteins are primarily build of long 6 2 anti-parallel coiled-coil arms, a globular hinge (situated in the middle of their peptide chain) 6 3 4...

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“…Consistent with our observation, coiled-coil free regions are predicted to increase a local flexibility in the arm 12 . The presence of the elbow-like structure was also reported for the SMC family proteins and this morphological characteristic is implicated in their actions on DNA 22 .…”

Section: Resultsmentioning

confidence: 61%

Rad50 zinc hook functions as a constitutive dimerization module interchangeable with SMC hinge

et al. 2020

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The human Mre11/Rad50 complex is one of the key factors in genome maintenance pathways. Previous nanoscale imaging by atomic force microscopy (AFM) showed that the ringlike structure of the human Mre11/Rad50 complex transiently opens at the zinc hook of Rad50. However, imaging of the human Mre11/Rad50 complex by high-speed AFM shows that the Rad50 coiled-coil arms are consistently bridged by the dimerized hooks while the Mre11/Rad50 ring opens by disconnecting the head domains; resembling other SMC proteins such as cohesin or condensin. These architectural features are conserved in the yeast and bacterial Mre11/Rad50 complexes. Yeast strains harboring the chimeric Mre11/Rad50 complex containing the SMC hinge of bacterial condensin MukB instead of the RAD50 hook properly functions in DNA repair. We propose that the basic role of the Rad50 hook is similar to that of the SMC hinge, which serves as rather stable dimerization interface.

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A folded conformation of MukBEF and cohesin

Cited by 132 publications

References 91 publications

A role of the Nse4 kleisin and Nse1/Nse3 KITE subunits in the ATPase cycle of SMC5/6

A role of the Nse4 kleisin and Nse1/Nse3 KITE subunits in the ATPase cycle of SMC5/6

A role of the Nse4 kleisin and Nse1/Nse3 KITE subunits in the ATPase cycle of SMC5/6

Rad50 zinc hook functions as a constitutive dimerization module interchangeable with SMC hinge

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