Enzyme Could Aid Cancer Fight

Teams at Cardiff University, Wales, and the University of Edinburgh, Scotland, who discovered a gene repair mechanism called the MBD4 enzyme in 1999, have now found that gene mutations are up to three times more common in mice lacking the MBD4 enzyme.

The findings of the research, led by Professor Adrian Bird of the Institute of Cell and Molecular Biology at Edinburgh and Professor Alan Clarke in the School of Biosciences at Cardiff, will be published in the journal Science on Friday 19 July.

Around 35,000 protein-coding genes are involved in the design of our bodies. All of these genes are present in every cell of the body, but not all of them are active or 'expressed' (able to build proteins). The pattern of active genes in a particular cell will determine its characteristics.

Different combinations of genes will, for example, be expressed in heart cells and liver cells, but patterns will also differ between healthy skin cells and cancerous skin cells.

Gene mutations can be caused by environmental factors such as cigarette smoke or sunlight, but, surprisingly, much gene damage is caused by the risky natural chemistry that goes on in the cells of our bodies. Genes carry the instructions for making proteins, which perform the essential processes of life, but many serious diseases like cancer are caused by accidental changes in these instructions which stop the resulting protein from doing its job properly.

The riskiest process of all is the practice of shutting down genes (so that they do not make their proteins) by marking them with chemical switches called methyl-groups. They work well for gene silencing, but in doing so they greatly increase the chances of mutation. One in three genetic changes that cause human disease can be attributed to methyl groups. No amount of care in avoiding harmful agents in food or air can escape this problem, which goes with being alive. The researchers have discovered that the MBD4 enzyme tries to repair the damage caused by methyl-groups before it can do harm.

Professor Clarke said: "It is very likely the MBD4 is a key defence against self-inflicted gene damage in humans. Humans are complicated chemical machines, and we have evolved to use certain chemical tricks to control gene expression - which unfortunately have a significant down-side in terms of gene damage. As humans we therefore had to invent a tool kit to repair the damage, and what we show here is that loss of part of that tool kit can increase the risk of developing cancer."