Core 2: Mammalian Artificial Chromosome (MAC)

哺乳动物人工染色体(MAC)核心将支持整个项目，该项目旨在解决 DNA损伤对细胞和动物的下游后果、原因和后果 染色体在细胞分裂时的错误分离，以及在肿瘤中驱动这些过程的机制。会的 作为Mac的代工厂，支持每个需要染色体的单独项目 操作和工程：从定点和可诱导的DNA损伤，到染色体报告 分离错误，以容纳化学遗传学工具箱的遗传编码组件。Mac电脑可以 携带大量(即100-2000 kb)基因有效载荷，并以分子的形式存在于细胞中，这些分子 与自然染色体一起遗传的。它们的自主性是一个关键优势，因为它们提供了 它们的基因有效载荷不会插入或以其他方式破坏宿主基因组。核心将采用我们最新的 MAC技术的创新催生了新一代MAC模板，我们在这些模板中 着丝粒染色质的种子。这种方法允许在不同的DNA模板上有效地形成MAC。 核心将采用MAC方法，从设计、创建、交付到电池、表征、 通过它们的实施，为个别项目中的实验计划提出建议。具体来说， Core将开发和使用以下类别的Mac：作为DNA目标的Mac 损伤，其中包含精心设计的基因有效载荷，将通过高水平的 复杂程度，以及携带染色体错误分离的荧光报告的那些。媒体宣传委员会 CORE旨在灵活地帮助项目成员开发新的实验路线，这些实验源于 在整个计划的初始步骤中取得的结果。

The mammalian artificial chromosome (MAC) Core will support the overall Project, which seeks to address the downstream consequences in cells and animals of DNA damage, the causes and consequences of chromosome missegregation at cell division, and the mechanisms that drive these processes in tumors. It will serve as a foundry for MACs that will support each of the individual projects that require chromosome manipulations and engineering: from site-directed and inducible DNA damage, to reporters for chromosome segregation errors, to housing the genetically encoded components of a chemical genetics toolbox. MACs can carry large (i.e. 100-2000 kb) genetic payloads, and exist in cells as molecules that are propagated and inherited alongside the natural chromosomes. Their autonomous nature is a key advantage, since they deliver their genetic payloads without insertion or other disruption of the host genome. The Core will employ our recent innovations in MAC technology that gave rise to a new generation of MAC templates in which we direct the seeding of centromeric chromatin. This approach permits efficient MAC formation on diverse DNA templates. The Core will undertake MAC approaches from their design, creation, delivery into cells, characterization, through to their implementation for experiments proposed in the individual Projects of the program. Specifically, the Core will develop and use MACs that fall into the following categories: ones that serve as targets for DNA damage, ones that harbor elaborate genetic payloads that will modulate chromosome segregation with a high degree of sophistication, and ones that carry fluorescent reporters of chromosome missegregation. The MAC Core is designed to be flexible to help Project members develop new lines of experimentation that arise from the findings achieved during the initial steps in the overall program.