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

DNA 回文：结构上矛盾的 D 的作用、后果和影响

• 批准号: 7536187
• 负责人: Susanna Maxwell Lewis
• 金额: $ 2.3万
• 依托单位: FEDERATION OF AMER SOC FOR EXPER BIOLOGY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7536187
• 关键词: Animal Model; Biochemical Genetics; Chromosomal Rearrangement; Chromosome Arm; DNA; Disease; Gene Amplification; Gene Deletion; Genetic; Genome; Genome Stability; Human; Human Genome; Iceberg; In Vitro; Investigation; Link; Metabolism; Mutation; Participant; Pattern; Personal Satisfaction; Range; Research; Role; Syndrome; Trinucleotide Repeats; Uncertainty; cancer cell; cancer genome; coping; human disease; single molecule; structural genomics; telomere; tumor progression; tumorigenesis

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.

描述（由申请方提供）：DNA回文突变引起严重的染色体重排，包括基因扩增、端粒代谢缺陷和整个染色体臂丢失以及较小的灾难性畸变。人类基因组中的天然回文酶与三种遗传综合征中的特定易位和导致某些地中海贫血的大基因缺失有关。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，这些回文区域以疾病特异性模式出现。回文结构的形成是肿瘤发生的早期阶段还是肿瘤进展的一个因素尚不清楚，但这种关联确定了研究的重要领域。 本次会议将吸引需要科普与palinoblasts相关的技术障碍的参与者（这肯定会在癌症基因组计划中出现）以及在palinoblasts的遗传，生物化学，结构和基因组影响方面做出最新进展的工作者。我们的演讲者涵盖了从体外单分子研究到模型生物到人类的广泛范围。 由于回文一直是一个棘手的目标，毫无疑问，在疾病中发挥作用的病例只是冰山一角。具有固有结构替代物的DNA可以从根本上致突变的概念是对三联体重复DNA的广泛接受的观察。正如三重重复不稳定性领域是活跃的，足以支持一个大型的专门会议，每年左右，我们预测，DNA回文将脱颖而出，作为一个明确的和令人兴奋的研究课题。拟议的会议是一个非常需要的机会，专注于回文对DNA代谢和突变的影响，并从那里探索DNA回文在基因组稳定性和人类疾病中的作用。