International collaboration on cancer
Children’s Medical Research Institute scientists have worked on an international effort with researchers in London and Boston to make a discovery that could impact cancer and ageing.
Doctors Tony Cesare and David Van Ly of the Genome Integrity Unit at the Children’s Medical Research Institute in Westmead are part of the team that published this discovery in the prestigious journal Nature. The project was led by scientists from the Crick Institute in London and includes input from Harvard University in Boston.
For decades scientists have known that telomeres, the protective caps at chromosome ends, are involved in aging and cancer. What they haven’t completely understood is how changes in telomere protection impact cancer and ageing.
Scientists have theorized for several years that a lasso-like structure at the very chromosome end, called a “telomere-loop”, may protect telomeres. Recently, doctors Cesare and Van Ly showed this is very likely true.
However, a puzzle piece was missing. A difficulty is presented if telomeres are protected by t-loops, as this can only work if t-loops are quickly opened and closed in a controlled way to allow the telomeric DNA to be copied before a cell divides.
This latest publication has identified how a telomere protein is altered during a specific window of the cell division cycle to open and close t-loops in a timely fashion. By adding or removing a modification to the telomere protein, TRF2, another protein, called RTEL1, comes to the chromosome end to open t-loops and allow the telomere to be replicated. Further, the team identified that disturbing the modification of TRF2 had profound affects that led to changes in the DNA throughout the genome.
“We were delighted to take part in this international collaboration that revealed the answer to a long-standing problem in cell biology,’’ Dr Cesare said. “We are now exploring how to use this knowledge in the future to benefit patients”.
This discovery has potential consequences to ageing, cancer, and a rare genetic disease called Hoyeraal-Hreidarsson Syndrome, where individuals are born with altered telomeres. The effects on human health and disease are being explored further.