A Protein Complex That Untangles DNA

An adult human consists of about 50,000 billion cells, 1% of which die and are replaced by cell division every day. In order to ensure cell survival and controlled growth of these new cells, the genetic information, stored in DNA molecules, must first be correctly copied and then accurately distributed during cell division. Moreover, to fully ascertain that the new cells will contain the same genetic information as the parental cells, any damage to the DNA, which is organised into several chromosomes, must be repaired.

"A cancer cell often has chromosomal aberrations that can be linked to erroneous copying, separation, or repair of the DNA molecule. By learning about the normal mechanisms that maintain a stable genome we can gain a better position to understand what goes wrong in cancer", says Camilla Sjögren, who leads the research group.

Central to both chromosome repair and distribution during cell division are three related protein complexes.

"Quite a bit is known about two of these complexes. One of them, cohesin, keeps the DNA copies together such that they do not separate too early; while the other, condensin, makes the chromosomes more compact, making the separation easier", says Camilla Sjögren.

The research group has studied the third, less well understood, protein complex, known as the Smc5/6 complex. This protein complex was found to bind to locations on the DNA strand that the researchers had artificially damaged, suggesting that it is directly involved in the repair process. Moreover, the Smc5/6 complex also seems to be required for the disentanglement of undamaged chromosomes before cell division. If these tangles, which are a natural consequence of the DNA copying process, are left unresolved the chromosomes cannot be separated and sent to the two nascent daughter cells. Like in the repair process, the Smc5/6 complex appears to resolve these intertwines by direct interaction with the DNA molecules, but this process is differently regulated as compared to the function in repair.

"Evidence points to that the Smc5/6 complex work in two different pathways, one needed for repair and the other for untangling. We now aim to study how this works on a molecular level. This will bring us one step closer to the general goal – a summary of the many mechanisms that collaborate to maintain our genetic stability", says Camilla Sjögren.