Understanding DNA packaging inside cells

Francis Crick Institute scientists have described the mechanism by which DNA enters and exits the protein rings that enable it to be packaged into the tiny nucleus inside each of our cells.

Frank Uhlmann of the Crick (currently based at Lincoln's Inn Fields) explained: "Our genome consists of four metres of DNA packed into a cell nucleus that is measured in micrometers. This packaging task is equivalent to stowing the 401 kms of the London Underground network in a suitcase.

"The means by which this becomes possible are the little ring-shaped protein machines in the nucleus, the 'SMC complexes'. They encircle the DNA strand at specific locations to establish the connections within and between DNA strands that organise the genome."

The scientists carried out their work in yeast. They began by purifying one of three SMC complexes found in yeast cells - known as the 6-subunit cohesin complex - together with a related protein called the 'cohesin loading complex'. It was the first time that this has been successfully done. The team then combined these purified proteins with DNA to biochemically reconstitute the loading and unloading of the cohesin rings onto DNA. This allowed them to define the path by which the DNA enters and exits the protein ring.

Dr Uhlmann said: "Chromosomes arguably are one of the most important biological structures and they have become an iconic symbol of the life sciences. To explain the molecular make-up and functioning of a chromosome is an important conceptual advance in its own right.

"In addition, it has huge biomedical implications, as SMC complex mutations are among the most frequent mutations found in cancer. Furthermore, inherited mutations in regulators of the SMC complexes are the cause for severe developmental disorders, including Cornelia de Lange Syndrome and Roberts Syndrome."

The paper, DNA Entry Into and Exit Out of the Cohesin Ring by an Interlocking Gate Mechanism, is published in Cell.

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