Biology subjects

Than, T.

Publications and source records attributed to Than, T..

2 recordsLinked to original sources

bioRxiv2022

Conformational dynamics of cohesin/Scc2 loading complex are regulated by Smc3 acetylation and ATP binding

The ring-shaped cohesin complex is the key player in sister chromatid cohesion, DNA repair, and gene transcription. The loading of cohesin to chromosomes requires the loader Scc2 and is regulated by ATP. This process is also hindered by Smc3 acetylation. However, the molecular mechanism underlying this inhibition remains mysterious. Here we identify a novel configuration of Scc2 with pre-engaged cohesin and reveal dynamic conformations of the cohesin/Scc2 complex in the loading reaction. We demonstrate that Smc3 acetylation blocks the association of Scc2 with pre-engaged cohesin by impairing the interaction of Scc2 with Smc3s head. Lastly, we show that ATP binding induces the cohesin/Scc2 complex to clamp DNA by promoting the interaction between Scc2 and Smc3 coiled coil. Our results illuminate a dynamic reconfiguration of the cohesin/Scc2 complex during loading and indicate how Smc3 acetylation and ATP regulate this process.

biochemistry↗

bioRxiv2018

A folded conformation of MukBEF and Cohesin

Structural maintenance of chromosomes (SMC)-kleisin complexes organize chromosomal DNAs in all domains of life, where they have key roles in chromosome segregation, DNA repair and regulation of gene expression. They function through topological entrapment and active translocation of DNA, but the underlying conformational changes are largely unclear. Using structural biology, mass spectrometry and cross-linking, we investigated the architecture of two evolutionarily distant SMC-kleisin complexes: proteobacterial MukBEF and eukaryotic cohesin. We show that both contain a dynamic coiled-coil discontinuity, the elbow, near the middle of their arms that permits a folded conformation. Bending at the elbow brings into proximity the hinge dimerization domain and the head/kleisin module, situated at opposite ends of the arms. Our findings favor SMC activity models that include a large conformational change in the arms, such as a relative movement between DNA contact sites during DNA loading and translocation.

molecular biology↗