Camilla Björkegren's Group
Chromosome dynamics and genome stability
The molecular mechanisms that control chromosome dynamics and maintain genome stability are essential for life and prevent accumulation of disease-promoting chromosomal aberrations. With the aim to decipher these mechanisms, our projects focus on the evolutionary conserved family of SMC protein complexes (SMC: Structural Maintenance of Chromosomes) which we investigate using the budding yeast Saccharomyces cerevisiae model organism, and biochemical and structural in vitro analysis.
Considered as an entity, the eukaryotic complexes cohesin, condensin and the Smc5/6 complex control most chromosome-based processes, including replication, segregation, repair and transcription. While it has become increasingly clear that SMC complexes act by structurally organizing chromosomes, their exact modes of action remain unclear. This is especially true for the Smc5/6 complex, which is the main object of investigation in our team.
The Smc5/6 complex has mainly been functionally connected with DNA repair and recombination, and we have analyzed this function in both mitotic and meiotic cells. We have also shown that Smc5/6 has a non-repair function, and accumulates on replicated chromosomes in unchallenged cells. Intriguingly, this enrichment increases in linear correlation with the length of the chromosomes, and our investigations show that this is due to a functional connection between the Smc5/6 complex and DNA supercoiling. Supercoiling is the under- or over-twisting of the DNA double helix, and arises when the replication or transcription machineries pry the helix apart. If enzymes called topoisomerases do not remove the supercoils, they inhibit replication and transcription, and increase the risk of genomic instability. Our ongoing investigations aim to understand how transcription- and replication-induced supercoiling influences the function of SMC complexes, chromosome dynamics and genome stability. We also investigate the role of Smc5/6 and supercoiling in the control of Hepatitis B virus and that of DNA supercoiling and topoisomerases in segregation of mitochondrial DNA in a collaborative project headed by Dr. Maria Falkenberg at Gothenburg University.
Perform your master thesis project with us
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DNA Supercoiling, Topoisomerases, and Cohesin: Partners in Regulating Chromatin Architecture?
Björkegren C, Baranello L
Int J Mol Sci 2018 Mar;19(3):
Sister Chromatid Cohesion Establishment Factor ESCO1 Operates by Substrate-Assisted Catalysis.
Kouznetsova E, Kanno T, Karlberg T, Thorsell AG, Wisniewska M, Kursula P, et al
Structure 2016 05;24(5):789-796
The Smc5/6 Complex Is an ATP-Dependent Intermolecular DNA Linker.
Kanno T, Berta DG, Sjögren C
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.
Jeppsson K, Carlborg KK, Nakato R, Berta DG, Lilienthal I, Kanno T, et al
PLoS Genet. 2014 Oct;10(10):e1004680
The maintenance of chromosome structure: positioning and functioning of SMC complexes.
Jeppsson K, Kanno T, Shirahige K, Sjögren C
Nat. Rev. Mol. Cell Biol. 2014 Sep;15(9):601-14