The SMC complexes, DNA and chromosome topology: right or knot?

Abstract

Topology is the study of geometric properties that are preserved during bending, twisting and stretching of objects. In the context of the genome, topology is discussed at two interconnected and overlapping levels. The first focuses the DNA double helix itself, and includes alterations such as those triggered by DNA interacting proteins, processes which require the separation of the two DNA strands and DNA knotting. The second level is centered on the higher order organization of DNA into chromosomes, as well as dynamic conformational changes that occur on a chromosomal scale. Here, we refer to the first level as "DNA topology", the second as "chromosome topology". Since their identification, evidences suggesting that the so called structural maintenance of chromosomes (SMC) protein complexes are central to the interplay between DNA and chromosome topology have accumulated. The SMC complexes regulate replication, segregation, repair and transcription, all processes which influence, and are influenced by, DNA and chromosome topology. This review focuses on the details of the relationship between the SMC complexes and topology. It also discusses the possibility that the SMC complexes are united by a capability to sense the geometrical chirality of DNA crossings.

Biophysics of protein–DNA interactions and chromosome organization

“…Via interactions with a third “kleisin” protein, SMC dimers form a tripartite ring structure that can encircle DNA, indicating a topological element to their DNA-organizing functions [101, 102, 103]. Furthermore, eukaryote SMCs appear to favor formation of right-handed DNA loops (loops with positive DNA writhe) [104, 105, 106, 107]. …”

The Escherichia coli SMC Complex, MukBEF, Shapes Nucleoid Organization Independently of DNA Replication

“…Others have proposed functions of SMC complexes in global compaction through bridging or SMC ring-mediated looping (4,5,12,15,25), while linkage between chromosomal regions has been proposed as a mechanism for the action of condensin in mitotic chromosomes (4). A global action on chromosomes has also been suggested for MukBEF and other SMCs through an effect on DNA topology, potentially facilitating compaction and segregation (3,16,29).…”

Dynamic localization of SMC5/6 complex proteins during mammalian meiosis and mitosis implies functions in distinct chromosome processes

“…However, an alternative possibility recently proposed assumes that MSCI represents the maintenance of a prior repressed state (Page et al, 2012). Given that the SMC5/6 complexes may have a role in chromosome topology (Carter and Sjögren, 2012), it is possible that these complexes could mediate the changes in chromatin conformation that occur at the sex body.…”

“…In eukaryotes, SMC proteins form heterodimers which associate with different non-SMC proteins to form holocomplexes that regulate different aspects of chromosome biology during both mitosis and meiosis (Carter and Sjögren, 2012). There are three distinct SMC complexes in eukaryotes.…”