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

描述(申请人提供)：DNA回文引起大量染色体重排，包括基因扩增、端粒代谢故障、整个染色体臂的丢失以及较少的灾难性异常。人类基因组中的自然回文与三种遗传综合征中的特定易位有关，也与导致某些地中海贫血症的大基因缺失有关。在癌细胞的基因组中观察到了新的回文区域的获得，值得注意的是，这些区域是以疾病特有的模式出现的。回文的形成是肿瘤发生的早期步骤，还是晚期肿瘤进展的一个因素尚不清楚，但这种联系为研究确定了重要的领域。 本次会议将吸引需要应对与回文有关的技术障碍(肯定会出现在癌症基因组倡议中)的与会者，以及在回文的遗传、生化、结构和基因组影响方面做出最新进展的工作人员。我们的演讲者涵盖了从单分子体外研究到生物模型再到人类的广泛范围。 由于回文长期以来一直是一个难以对付的目标，毫无疑问，被证明在疾病中发挥作用的病例只是冰山一角。具有固有结构替代的DNA可以从根本上具有突变性，这一观点在三联体重复DNA中得到了广泛的接受。就像三重重复不稳定场足够活跃，足以支持每年一次的大型专门会议一样，我们预测DNA回文将作为一个明确和令人兴奋的研究主题脱颖而出。拟议中的会议是一个非常必要的机会，可以集中讨论回文对DNA新陈代谢和突变的影响，并从那里探索DNA回文在基因组稳定和人类疾病中的作用。

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.