Final Report Summary - DISENTANGLE (Untangling the Bacterial Chromosome: Condensin's Role in Sister Chromosome Separation and its Mechanisms.)
Failures in chromosome segregation give rise to cells or gametes with an abnormal number of chromosomes. Aneuploidy is a common cause of genetic disorders and aneuploid cells likely serve as precursors in the development of many cancers, highlighting the medical relevance of genome stability and maintenance. Chromosome segregation depends on a set of structural maintenance of chromosomes (SMC) protein complexes that help transform chromosomes into distinctive, compact shapes during mitosis allowing them to be correctly segregation before cell division. Cohesin specifically links sister chromatids together. Condensin is thought to preferentially or exclusively build intra-chromatid tethers thereby somehow promoting the length-wise condensation of chromatids.
We are studying the bacterial and archaeal ancestor of cohesin and condensin, called prokaryotic condensin, with the aim to shed light on fundamentally conserved aspects of the molecular action of SMC protein complexes. Our work was focused on understanding the molecular architecture of SMC complexes, its association with the chromosome and the role of conformational changes during chromosomal loading. We have established the tripartite annular architecture of the prokaryotic SMC complex and its interaction with the bacterial chromosome by entrapment of the DNA double helix. Furthermore, our work has revealed a large-scale conformational change from a rod shaped to a more open ring-like structure as fundamental basis for the regulation of its physical association with DNA and the chromosomal loader complex.
Our findings support the notion that all SMC complexes operate using fundamentally related molecular mechanisms and thus have the potential to provide basic understanding of the molecular action of cohesin and condensin in eukaryotes. These insights form a vital basis for further studies on how SMC complexes brings about the massive condensation of DNA within chromosomes that is needed for their compaction and accurate segregation during cell division.
We are studying the bacterial and archaeal ancestor of cohesin and condensin, called prokaryotic condensin, with the aim to shed light on fundamentally conserved aspects of the molecular action of SMC protein complexes. Our work was focused on understanding the molecular architecture of SMC complexes, its association with the chromosome and the role of conformational changes during chromosomal loading. We have established the tripartite annular architecture of the prokaryotic SMC complex and its interaction with the bacterial chromosome by entrapment of the DNA double helix. Furthermore, our work has revealed a large-scale conformational change from a rod shaped to a more open ring-like structure as fundamental basis for the regulation of its physical association with DNA and the chromosomal loader complex.
Our findings support the notion that all SMC complexes operate using fundamentally related molecular mechanisms and thus have the potential to provide basic understanding of the molecular action of cohesin and condensin in eukaryotes. These insights form a vital basis for further studies on how SMC complexes brings about the massive condensation of DNA within chromosomes that is needed for their compaction and accurate segregation during cell division.