Cellular alarm bell secrets uncovered
9 Sep 2009 by Evoluted New Media
Scientists have discovered how cells react to a molecular ‘alarm bell’ that goes off when their DNA is damaged.
Scientists have discovered how cells react to a molecular ‘alarm bell’ that goes off when their DNA is damaged.
Our genome is constantly under attack from things like UV light and toxins, which can damage or even break DNA strands and ultimately lead to cancer and other diseases. Scientists have known for a long time that when DNA is damaged, a key enzyme sets off a cellular ‘alarm bell’ to alert the cell to start the repair process, but until recently little was known about how the cell detects and responds to this alarm.
In a study published in Nature Structural and Molecular Biology, researchers at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, have identified a whole family of proteins capable of a direct response to the alarm signal.
Scientists have known for 50 years that one component of chromatin – the complex created when DNS is folded in a cell - an enzyme known as PARP1, is activated by DNA damage and produces a molecular signal, called PAR. Andreas Ladurner and colleagues at EMBL have identified a whole family of proteins that respond to this signal by binding to it directly.
What these proteins share is a special region called a macrodomain. Among the members of the family the researchers found a protein called histone macroH2A1.1. “This was very surprising. Histones play a major role in assembling chromatin and keeping it together, but they don’t usually have macrodomains,” said Ladurner. “The finding is particularly relevant, because it turns out that cancer cells don’t have macroH2A1.1. The fact that one member of the rapid response team that detects DNA damage is missing could contribute to the disease.”
Because macroH2A1.1 is embedded in chromatin, when it recognises PAR at DNA damage sites, it drags the complex but highly-organised tangle of chromatin with it. As a result, macroH2A1.1 condenses the chromatin environment around the damaged area.
The scientists are now trying to understand why this happens. One plausible explanation could be that by temporarily compacting the DNA, the broken ends of the DNA molecule are kept closer together. This should increase the chances of being able to repair it.
