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Laboratory of Structural Proteins of Eukaryotic Chromosomes

How to fit a long DNA string into a small nucleus?

Chromosomes reside in the cell nucleus. However, the length of human DNA molecules is 10000 times bigger than the space of the nucleus. To help billions of bases fit into the small nucleus, histone and other chromatin-associated proteins come and fold DNA into condensed fibers. The SMC (Structure maintenance of chromosome) complexes are the key components of higher-order chromatin fibers and play important roles in genome stability. They are conserved from bacteria to humans. Three SMC complexes are present in most eukaryotic cells: cohesin (SMC1/3), condensin (SMC2/4) and SMC5/6 complex. Cohesin can make internal loops or embrace two sister chromatids (feature essential for proper chromosome segregation). Condensin interconnects loops to condense chromatin during mitosis. The SMC5/6 complex is involved in the homologous recombination-based DNA repair, in replication fork stability and processing, and in cohesin regulation.

We study assembly and functions of protein complexes (particularly, SMC5/6 complex). We use combination of genetic (fission yeast model), biochemical (mostly yeast two-hybrid system and other binding assays) and bioinformatics methods to get deep insights into their features (particularly protein-protein and protein-DNA interactions). Recently, we discovered several important features of the Nse3 (non-SMC element) KITE subunit of the SMC5/6 complex: its role in structural organization of the SMC5/6 complex, its DNA-binding ability, its evolution from bacteria to novel mammalian (MAGE) protein family. In addition, we participated in characterization of new human chromosome breakage syndrome associated with Nse3 mutations.

Collaborations

To be able to cover a broad field of chromosome biology, biochemistry of proteins and their complexes, we collaborate with groups inside as well as outside of our university. Particularly, we have long-term collaboration on the SMC5/6 complex with Alan Lehman, Tony Oliver and Jo Murray at Sussex University. We discovered close relation of eukaryotic SMC5/6 and bacterial SMC complexes together with Stephan Gruber. Further, we explore beauty of many more complexes in collaboration with bioinformaticians Bara Kozlikova and Ivan Viola.

Operating under NCBR