New links established between DNA damage and tumour suppression!

p53   encoded by the TP53 gene is very important in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer. As such, p53 has been described as "the guardian of the genome".
However recently NCI scientists have linked p53  with TRF2, a protein that forms a complex that protects the ends of chromosomes from undergoing erosion. The ends of chromosomes are known as telomeres, and these end-pieces have been shown to influence cell longevity as well as cancer.  While activated p53 can be an indicator of DNA damage due to telomere malfunction, this study is the first to show that p53 also functions by negatively regulating the telomere-binding protein TRF2, thus suggesting the presence of a novel feedback loop. The study, lead by Curtis C. Harris, M.D., with coworkers Kaori Fujita, Ph.D., and Izumi Horikawa, M.D., of the Laboratory of Human Carcinogenesis, Center for Cancer Research.
Telomeres are capped at each end to protect them from degrading and from being recognized as damaged DNA. At the end of their lifespan, telomeres lose this protection and DNA-damage signaling pathways are triggered that activate p53. Harris and his team found that p53 controls TRF2 levels, through an intermediary component known as Siah-1. In this experiment, TRF2 was found to be repressed and Siah-1 was induced in normal human tissue cells when p53 was activated. The scientists also found that p53 affects DNA damage signaling from uncapped telomeres, as well as regulating the telomere-capping complex. This suggests that the p53-Siah-1-TRF2 pathway plays an integral part in orchestrating the DNA damage response of telomeres. Both p53 and telomeres have therapeutic significance in cancer. This discovery, therefore, provides not only a new mechanistic insight into p53- and telomere-based cancer therapeutics currently used or tested, but also the experimental basis for the development of new therapies, according to the scientists.
This can later prove to be a landmark link in cancer therapies.