New chromatin studies reveal 'more realistic' structure for DNA in replicating chromosomes
Spanish researchers have proposed a new model for DNA packaging during cell division. They say replicating chromosomes form dense, plate-like structures - not fibres as previously thought - which may also account for the characteristic banding seen in chromosome preparations.
Chromosomes in dividing cells are widely thought to be made up of chromatin fibres - DNA wound around protein particles known as nucleosomes. But, say researchers at the University of Barcelona, such loose packaging can’t explain the high concentration of DNA inside replicating chromosomes.
’Many, many papers explain things based on this old point of view,’ says lead researcher Joan-Ramon Daban. ’But to explain how the cell is able to keep DNA safe, to transfer it through the cell without damage, we need a strong, compact structure and we really think stacked plates are stronger than fibrous structures.’
The difference between Daban’s work and previous studies is that conditions in his team’s experiments more closely match those of the cell environment, which contains high concentrations of cations such as Mg2+. Instead of preparing the chromosomes for study by carrying out full denaturation using Mg2+ chelating agents such as EDTA, the team produced a partial denaturation by incubating chicken chromosomes at body temperature and then passing them through a syringe.
Frank Uhlman, who studies chromosome separation at Cancer Research UK’s London Research Institute, thinks the plates could be a fixation artefact. ’I have never seen them in any other chromosome preparation,’ he says.
But Daban argues that his team studied their chromosome preparations using several different techniques, including conventional transmission microscopy, cryo-electron microscopy and atomic force microscopy, only to be confronted with the same results - these dense, stacked plates. The results also support findings from a previous experiment in which the researchers discovered plates in human HeLa cells.
’I think Daban’s work has gone underappreciated for years,’ says Jeffrey Hayes, an expert in DNA structure at the University of Rochester Medical Center, New York. ’He has pointed out that the density of DNA in the metaphase chromosome is much higher than can be accounted for by current models for folding of the 30nm chromatin fibre. It’s a very interesting dilemma that needs further attention.’
Daban says no other realistic explanation has been provided for the discrete bands that form when chromosomes are dyed in preparation for genetic studies. With fibres, he says, it would be impossible to imagine how these bands could form. ’But if chromosomes are made of many stacked plates, then it’s easy to imagine that the dye goes to particular bands that are richer in A-T or G-C pairs.’
The next step is to try to understand what interactions hold the plates together. As yet, the team only know that interactions between plates are weaker than within them.
et alEur Biophys JDOI: 10.1007/s00249-008-0401-1