Camilla Sjögren's Group
The SMC complexes, chromosome dynamics and stability
The molecular mechanisms which maintain genome stability are essential for life and prevent accumulation of disease-promoting chromosomal aberrations. With the aim to decipher these mechanisms, our project focuses on the evolutionary conserved family of SMC protein complexes (SMC: Structural Maintenance of Chromosomes). There are three eukaryotic complexes: cohesin, condensin and the Smc5/6 complex. The majority of our ongoing investigations aim to disclose the function of the Smc5/6 complex, which is the least well understood. We do this using the budding yeast Saccharomyces cerevisiae as model organism.
The Smc5/6 complex has mainly been functionally connected with DNA repair and we have found that it is recruited to DNA breaks where it activates cohesin. We have also shown that Smc5/6 binds to chromosomes as a consequence of DNA replication. Intriguingly, the frequency of Smc5/6 binding sites increases in linear correlation with the length of chromosomes, and we have unraveled a function for Smc5/6 in the resolution of replication-induced topological tension. This tension arises when the replication machinery pries apart the parental double-helix into single DNA strands. If the tension is not removed, it will lead to replication fork blockage which increases the risk of genomic rearrangements. Our more recent results suggest that topological tension also could have a positive role in the organization of chromosomes, executed via the SMC complexes.
Our ongoing and future investigations are based on these findings, and the main objectives are to:
- Establish the molecular details of how the Smc5/6 complex removes topological tension and protects genome stability.
- Characterize the interplay between DNA topology and chromosomes structure, stability and dynamics.
|Andreas Kegel||Senior lab manager|
|Davide Berta||PhD student, Graduate Student|
|Kristian Jeppsson||PhD student|
|Martin Tran||PhD student, Graduate Student|
|Stefina Milanova||R&D trainee|
|Takaharu Kanno||Senior lab manager|
The Smc5/6 Complex Is an ATP-Dependent Intermolecular DNA Linker.
Cell Rep 2015 Sep;12(9):1471-82
The chromosomal association of the Smc5/6 complex depends on cohesion and predicts the level of sister chromatid entanglement.
PLoS Genet. 2014 Oct;10(10):e1004680
The maintenance of chromosome structure: positioning and functioning of SMC complexes.
Nat. Rev. Mol. Cell Biol. 2014 Sep;15(9):601-14
The SMC complexes, DNA and chromosome topology: right or knot?
Crit. Rev. Biochem. Mol. Biol. ;47(1):1-16