DNA Palindromes:Roles, consequences and implications of structurally ambivalent D

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DESCRIPTION (provided by applicant): DNA palindromes provoke gross chromosomal rearrangements including gene amplifications, faulty telomere metabolism, and loss of whole chromosome arms as well as less disastrous aberrations. Natural palindromes in the human genome have been linked to specific translocations in three genetic syndromes and to large gene deletions that cause certain thallasemias. Acquisition of new regions of palindromy has been observed in the genomes of cancer cells that, remarkably, arise in a disease-specific pattern. Whether palindrome formation is an early step in oncogenesis or a factor in later tumor progression is unclear, but the association defines important territory for investigation. This meeting will attract participants who need to cope with the technical barriers associated with palindromes (as will assuredly arise in the cancer genome initiative) as well as workers who have contributed recent advances in the genetic, biochemical, structural and genomic implications of palindromes. Our speakers cover a broad range from single molecule studies in vitro to model organisms to humans. Because palindromes have long been such an intractable target, there is no doubt that the cases where a role in disease is demonstrated represent just the tip of the iceberg. The notion that a DNA with inherent structural alternatives can be fundamentally mutagenic is an observation that is well accepted for triplet repeat DNA. Just as the triplet repeat instability field is active enough to support a large dedicated meeting every year or so, we predict that DNA palindromes will come into the fore as an explicit and exciting research topic. The proposed meeting is a much needed opportunity to focus upon the impact of palindromy on DNA metabolism and mutation, and from there to explore the role of DNA palindromes in genome stability and human disease.