Eugene Kim research group projects

SMC proteins

Figure 1. Real-time imaging of DNA loop extrusion mediated by condensin

Figure 2. Transition from a single loop to a Z-loop via condensin-condensin bypassing

Chromatin loops are one of the basic structural units of three-dimensional chromosome organization. Loops were hypothesized to form by ‘loop extrusion,’ by which structural maintenance of chromosomes (SMC) complexes bind a chromatin fiber and reel it in, extrude it as a loop. Recently, we provided direct evidence of DNA loop extrusion activity of condensin SMC complexes (Fig. 1) and their ability to bypass one another and generate higher-order loop structures (Fig.2 ). However, it still remains mysterious how these unique new classes of motor proteins carry out their loop extrusion activities at the molecular level. We hope to bridge this knowledge gap by obtaining hi-resolution structural information of the reaction intermediates via cryo-EM and cryo-electron tomography approaches.

Moving further, we are interested in investigating the roles of other SMCs and SMC-like (e.g. Rad50, RecN and Smc5/6) proteins in genome organization and maintenance.

References 

[1] E. Kim, J. Kerssemakers, I. A. Shaltiel, C. H. Haering, C. Dekker, DNA-loop extruding condensin complexes can traverse one another. Nature 579, 438–442(2020) 

[2] M. Ganji, I.A. Shaltiel*, S. Bisht*, E. Kim, A. Kalichava, C.H. Haering, C. Dekker, Real-time imaging of DNA loop extrusion by condensin. Science 360 102-105 (2018)

 

DNA supercoiling

Figure 1. DNA supercoil generated by DNA twisting

Figure 2. Movie showing proteins (red) binding on supercoiled DNA (green). Scale bar = 1µm

DNA in cells constantly undergoes topological stresses that are generated by genomic processes, such as transcription and replication. As a result, DNA takes a super-helical structure that is over- or under-wound, called DNA supercoils (Fig.1). While bacterial genomes are maintained in a globally negatively supercoiled (under-wound) state, DNA supercoiling in eukaryotes is enriched locally and correlated with transcriptionally active regions. Despite its potential importance in chromatin packaging and genome function, DNA supercoils and the associated biological processes remain largely unknown. We are interested in studying the interactions of supercoiled DNA with proteins (Fig.2) which can generate, modulate, and remove DNA supercoils by using single-molecule imaging and force-spectroscopic tools.

Further reading

[1] S.H. Kim*, M. Ganji*, E. Kim, J. van der Torre, E. Abbondanzieri, C. Dekker, DNA sequence encodes the position of DNA supercoilseLife 7:e36557 (2018) 

 

Chromosome resolution

When cells enter mitosis, interphase chromatins experience dramatic reshaping into compressed, cylindrical shape of chromosomes, followed by efficient segregation to daughter cells. Such structural changes comprise a range of different biochemical processes, including longitudinal condensation of the chromosome axis, loss of cohesion, resolution of sister chromatids, and individualization of chromosomes into separate bodies. We are broadly interested in understanding how the molecular mechanisms underlying these individual processes are coordinated to resolve sister DNAs into separate bodies.   

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