CANCER RESEARCH UK scientists have discovered a gene which prevents cells with faulty DNA passing on cancer-causing mistakes to new cells, according to a study published in Nature Cell Biology* today (Sunday).
Scientists from Cancer Research UK’s London Research Institute Clare Hall Laboratories, looked at frog cells to determine how cells organise their internal molecular machinery to prevent division when their DNA is faulty. This strategy prevents the accumulation of genetic mistakes in daughter cells which can cause cancer.
These genetic mistakes are the hallmark of cancer cells. If scientists can find out how these faults occur they could develop drugs which block cancer development.
Scientists already knew that two genes, ATM and ATR play a key role in the cells’ surveillance mechanism that prevents genetic damage. These genes coordinate cells’ responses to DNA damage. One of the ways that the cells respond to damage is to halt cell division.
This study identified that the ATM and ATR proteins act on a protein, Cep63, which builds an important part of the cellular machinery – called centrosomes. Centrosomes are responsible for accurate separation of duplicated chromosomes into daughter cells.
The Cancer Research UK scientists showed that ATM and ATR regulate Cep63 to ensure that only cells with undamaged DNA can assemble the cellular apparatus necessary to split the chromosomes into new cells.
Dr Vincenzo Costanzo, head of genome stability at the London Research Institute, said: “A cell needs to pass a series of checkpoints which assess if it is fit to live and divide. Cep63 is one of the key players in this judgement system which prevents cancer-causing faults in the cell’s DNA being passed on to new cells.
“Intriguingly, centrosome number and function is altered in aggressive tumours and these faluts have long been thought to be linked to human cancer.
“So if we can control Cep63 function at centrosomes we might be able to prevent the accumulation of cells with abnormal chromosomes typically found in tumours. Consistent with this theory it has recently been reported that the Cep63 protein is faulty in invasive tumours and aggressive leukaemias.”
Lesley Walker, Cancer Research UK’s director of cancer information, said: “This important research has uncovered a new tumour suppressor gene. Increased understanding of how the body naturally prevents cancer will help us develop better targeted treatments. These findings open up exciting avenues for research.”
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*An ATM- and ATR -dependent checkpoint inactivates spindle assembly by targeting CEP63. Eloise Smith et al. 1 February 2009. Nature Cell Biology.