One of the most fascinating aspects of the architecture of genomes is how long DNA molecules manage to fold in a highly ordered and compact fashion to form chromosomes. For example, in a human cell, the chromosomes are a few microns (millionths of a meter) in size but contain DNA molecules several centimeters long. To achieve this folding, the DNA is organized into thousands of loops, which allows the length of the DNA to be greatly reduced without limiting the accessibility of the genes it contains. Those responsible for generating these DNA loops in a regular and orderly manner are the SMC protein complexes (Structural Maintenance of Chromosomes), which have the ability to bind to any point on the DNA to extrude from that point. a DNA loop.
The exact operation of this DNA loop extrusion process is still unknown. However, it is known that this mechanism implies that the SMC complexes have to firmly grip the DNA on one side and actively push it on the other side, so that the DNA loop that forms can grow in size until it collides, for example, with the SMC complex of the neighboring loop.
A team from the Institute of Molecular Biology of Barcelona (IBMB), dependent on the Higher Council for Scientific Research (CSIC) in Spain, has discovered how condensin, an essential SMC complex in all eukaryotic cells, is capable of extruding DNA and producing thus the growth of ties.
The team, which includes Joaquim Roca, Belén Martínez, Silvia Dyson and Joana Segura, has discovered that, to produce the extrusion of loops, condensin interacts with DNA through three binding sites. The first of these sites serves to anchor one end of the DNA loop and the other two sites serve to grow the loop at the other end. To do this, these two sites are repeatedly moved towards and away from each other to produce tiny tweaks in the DNA. Each of these pinches becomes a small step that lengthens the size of the loop held by the first place. This mechanism for sliding DNA is very efficient as each pinch can span tens or hundreds of base pairs of DNA, yet it consumes very little energy.
chromosomes (Image: Joaquim Roca)
The key that has allowed this discovery has been that each pinch deforms the DNA forming a small left-handed loop, which can be detected and measured by laboratory techniques.
“SMC protein complexes are essential and highly conserved in all cells: eukaryotes, archaea, and bacteria. Possibly, these complexes appeared as soon as the problem of how to fold and organize the long DNA molecules that make up genomes arose. The loop extrusion mechanism seems to have been the optimal solution to this problem and therefore it has been maintained throughout evolution”, points out Joaquim Roca.
The study is titled “Condensin pinches a short negatively supercoiled DNA loop during each round of ATP usage”. And it has been published in the academic journal The EMBO Journal. (Source: CSIC)