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Evolution of human genome's 'guardian' gives people unique protections from DNA damage
Date:1/16/2008

chromosomes that help shield against damage. Shorter telomeres can make people more susceptible to chromosomal damage and increase our risk of developing malignant tumors. When genes replicate, the process does not copy the very ends of the gene, so telomeres act like caps on the ends of shoelaces, helping preserve DNA structure and preventing genetic unraveling and loss of genetic information.

A clue to p53 functional differences may be found in sunlight. Exposure to the ultra-violet rays in sunlight activates the DNA-damage responses of the repair gene (Ddb2) in humans, but the same gene does not function in rodents. Some studies have suggested that rodents may have a reduced need for genetic protection from sunlight because they are nocturnal and have a fur shield.

Although the full implications of these evolutionary points remain far from clear, our work demonstrates that there has been both refinement and evolution of gene networks controlled by p53, Dr. Aronow said. Exciting work is underway by research groups within the National Cancer Institutes Mouse Models of Human Cancer Consortium to develop mice that are genetically engineered to test the combined effects of altering p53 and telomerase, the enzyme that controls the length and stability of repeating DNA sequences in the telomere region. Mouse models will continue to become progressively more powerful tools for studying human cancer and additional information about the p53 network will help us refine our interpretation of pre-clinical research that may lead to improved cancer prevention for at-risk and normal individuals.

In conducting their analysis of p53 target genes, the international research team used comparative DNA sequence analysis and functional tests of highly engineered yeast and mouse cell culture assays to examine 47 established p53 response elements in 14 vertebrate and non-vertebrate species. The study included researchers from the National Institute for Cance
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Contact: Nick Miller
513-803-6035
Cincinnati Children's Hospital Medical Center
Source:Eurekalert

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