Researchers crack DNA riddle to show how process of mitosis works

Researchers have answered a fundamental question that has perplexed cell biologists for almost 150 years.   

Tom Collins, from Wellcome’s Genetics and Molecular Sciences team, explains why the discovery is so important and how the research team finally found what had evaded them for so long.

During development, and throughout our entire lives, most of our cells undergo a process called mitosis. This is fundamental to life and the process by which cells replicate and divide into two identical daughter cells. But when mitosis goes wrong, it can lead to birth defects and cancer.

So how do our cells replicate, then compact the huge amount of genetic information needed to make a human 10,000-fold, and accurately split it between two new cells?

We’ve all heard the statistic about how if you uncoiled all the DNA in all a human’s cells it would reach to the Sun and back several times over. But this disguises the reality of the challenge our cells face when they replicate.

During mitosis the entire genome must be reorganised to separate the replicated chromosomes into new nuclei. Chromosomes go from 23 pairs of relatively loosely packed DNA to incredibly dense, compacted structures before being separated into new cells.

For close to 150 years researchers have been able to take sequences of microscopy images of mitosis, so that we have built a detailed but incomplete picture of the stages of mitosis. In fact, chromosomes and mitosis were some of the earliest things we could see under a microscope, so scientists have been studying them for a long time.

What we didn’t understand was the process by which cells move from one stage of mitosis to the next. Until now.

Genetic material is folded in compacted loops

As with many of the major questions in biology, it has taken technological advances to find the answer to how cells condense vast amounts of DNA into tiny structures that can be separated.

In a new paper in the journal Science, Wellcome Principal Research Fellow Professor Bill Earnshaw and his team at the Cell Biology Centre in Edinburgh describe how they used an incredibly rigorous method to control the movement of cells from one stage of mitosis to another. This has given them a unique glimpse into the process as it occurs.

They show that genetic material is folded to form a series of compacted loops, which project out from a helix-shaped axis, like steps on a spiral staircase. These helical axes, combined with the loops of DNA, pack the genome into orderly structures that can be accurately split when cells divide. 

The discovery was possible due to international collaboration between three laboratories. Prof Earnshaw’s lab performed the biochemical experiments, whilst teams in the USA at MIT and the University of Massachusetts did the genomic chemistry and mathematical modelling required. 

What this discovery means

The first step to tackling diseases is to understand what happens in normal, healthy systems. This study tells us exactly that. We already know the consequences of errors in mitosis, and we’re now a step closer to understanding how these mistakes occur. 

The next steps for researchers could be to perform similar experiments in defective cells and tissues. This would help us to build up a detailed picture of how we might develop approaches to tackle defects. 

This discovery is the start of a long journey towards practical applications. But after 150 years of searching, scientists are understandably thrilled at this latest discovery. 

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