麻豆传媒

Don鈥檛 be fooled by p53鈥檚 humdrum name. Dubbed the 鈥済uardian of the genome鈥� for its role in keeping our cells from turning cancerous, protein 53 may also be necessary for sex.

The protein flits into action when cells in fruit flies, mice and probably humans replicate and divide their DNA in order to create new eggs and sperm 鈥� a process called meiosis 鈥� say a team led by , a molecular biologist at the University of Texas Southwestern Medical Center in Dallas.

Until now, it has been thought that p53鈥檚 only role is to protect cells from the DNA mutations that cause cancer: when DNA is under attack from mutation-inducing substances such as reactive oxygen species, cigarette smoke or radiation, the protein starts a chain of events that either repairs the damage or instructs the cell to stop dividing, or even to end its own life.

The gene that produces p53 is mutated in about half of all cancers, while related genes are probably disturbed in the other half, Abrams says. 鈥淚t鈥檚 probably the most widely studied protein on the planet,鈥� he adds.

But there鈥檚 a paradox. 鈥淚t鈥檚 pretty clear that p53 exists in organisms that don鈥檛 get cancer 鈥� in very short-lived animals where tumour suppression would never be an evolutionary pressure,鈥� he says.

Green protein

One example is the common fruit fly Drosophila melanogaster, a stalwart of genetics research, which makes its own version of p53. The protein kicks into gear when flies are exposed to very strong, DNA-damaging radiation, but Abrams and his colleague Wan-Jin Lu wanted to know when and where p53 is active in living flies under normal conditions.

They genetically engineered flies to produce a version of p53 that glows green, and were then able to observe that the protein was produced only in the egg chambers of female flies. There, its production was tightly coupled to that of a protein that breaks DNA strands in half to allow the reshuffling that occurs between maternal and paternal chromosomes during meiosis.

Such 鈥渞ecombinations鈥� endow each egg with a different mix of maternal and paternal genes to create genetic diversity. But when Abrams鈥檚 team looked at flies that don鈥檛 make functional p53, they found that these flies recombined their genomes during meiosis far less often than normal flies.

Further tests on mouse tissue confirmed that p53 plays a similar role in mammals 鈥� strong evidence that it probably does this in humans too, says Abrams.

Meiosis watchdog

Abrams suggests that p53鈥檚 original role was to control recombination during meiosis. 鈥淟ater it became co-opted for the purposes of tumour suppression,鈥� he says.

The two roles may not be completely unrelated. Abrams says p53 may act as a 鈥渨atchdog鈥� during meiosis, eliminating cells where repair doesn鈥檛 occur 鈥� a job that isn鈥檛 so different from monitoring the kind of DNA damage that leads to cancer.

鈥淭he current paper is nice,鈥� says , one of the discoverers of p53 in 1979 and now at the Institute of Molecular and Cell Biology in Singapore. Last year, his team found that that ancient single-celled eukaryotes called placozoans also produce the protein. However, he is not convinced that its original role was in meiosis.

Abrams concedes that p53鈥檚 already daunting workload could soon grow. 鈥淪omebody could come along tomorrow and find something else that鈥檚 equally compelling.鈥�

Journal reference: , DOI: 10.1126/science.1185640