A biological catalyst that many hoped would prevent cancer, could actually promote it, new research in Nature1suggests. Telomerase, the enzyme that normally repairs the ends of our chromosomes, may sometimes be too slow and may thus allow cancer to develop, say Ronald DePinho of the Harvard Medical School and his colleagues.

DNA damage can cause cancer. DNA is stored in the chromosomes, and each time a cell divides the chromosomes get eroded at each end. The consequences when these ends or 'telomeres' get too short can be drastic.

Pieces of chromosomes may break off and be destroyed, or become attached to other chromosomes. The damage gets worse as the cells replicate further. This plays havoc with the functions of the genes encoded by the DNA, giving rise to cells that grow and spread uncontrollably.

Mice and humans suffer from different types of cancer. Mice have long telomeres that are resilient to cell division, unlike human telomeres. So it was thought that mice mainly suffer from cancers that are not related to telomere damage.

DePinho's team worked with mutant mice lacking the telomerase gene. They shortened the animals' telomeres by inter-breeding them for several generations. To make the mice cancer-prone, the researchers also knocked-out gene which is responsible for limiting DNA damage, 'p53'.

Mice lacking both p53 and telomerase suffered mainly from malignancies of body linings, or 'epithelia', such as the gut wall. 80% of human cancers start in the epithelia. Mice lacking only p53 developed different cancers, the researchers report.

This appears to show that telomerase deficiency -- and the resulting telomere damage -- causes cancer. But cells in human cancers often have high amounts of telomerase -- which has lead some researchers to invest in developing strategies for lowering telomerase.

DePinho's group speculates that cancer cells recognize that their telomeres have been damaged and make more telomerase. But this makes the situation worse, not better, the researchers propose. The telomerase actually stabilizes the cancer cells by preventing further chromosome damage that would ultimately kill them.

Bert Vogelstein of the Johns Hopkins Oncology Center in Baltimore, Maryland, thinks this is fascinating research. "Telomerase appears to be a double-edged sword, there is no simple way to reconcile these completely opposite views of telomerase function [in cancer development]," he says.

Robert Newbold of Brunel University, UK is more cautious: "Mice aren't men. There are major differences between humans and rodents in telomerase regulation."

Evidently the end is not in sight for the telomerase story.