Structural basis of meiotic chromosome organization by the synaptonemal complex.

精子和卵细胞是人类新生命产生所必需的。它们是通过减数分裂产生的，减数分裂是一个细胞分裂的过程，在这个过程中，遗传信息被重组以增强多样性。受精后，精子和卵子中的DNA结合在一起，提供了完整的遗传信息，定义了一个独特的人类。虽然减数分裂的过程在概念上看起来很简单，但实际上它是一个复杂的过程，经常会出错，导致精子或卵子的染色体数量不正确，或者根本不产生生殖细胞，导致流产和不育。减数分裂的核心是配对染色体之间的基因交换过程。为了能够彼此对齐并交换遗传物质，每对匹配的染色体需要以特定的三维形状组织起来，这是减数分裂所特有的。先前的研究表明，一种称为联会复合体（SC）的大型蛋白质结构对此至关重要，它作为分子支架，以正确的方式将染色体固定在一起，以便进行DNA交换。虽然SC在减数分裂中的重要性已经被认识很久了，但我们仍然对SC的结构和功能知之甚少。我们计划通过研究SC复杂的分子结构来发现SC如何在减数分裂中发挥关键作用。我们的具体目标是精确地确定SC如何确定每个匹配染色体的形状，将其DNA折叠成配对，遗传交换和最终分离步骤所需的三维结构。我们将通过在SC的蛋白质构建块的原子分辨率下产生分子图像来实现这一点，这将显示它们如何与DNA以及彼此相互作用，以便为发生遗传交换建立正确的分子框架。我们对SC分子结构的研究将有助于我们了解其在减数分裂中的重要作用，并解释其组装缺陷如何导致不育，流产和遗传疾病。此外，我们的工作将提高我们对人类细胞处理大染色体DNA分子的不同方式的认识。这一信息很重要，因为在细胞增殖过程中，由于DNA包装缺陷而导致的染色体错误分选可能导致基因组发生不必要的改变，并导致癌症等疾病。

Sperm and egg cells are required for the generation of new human life. They are produced through meiosis, a process of cell division in which genetic information is reshuffled to enhance diversity. Upon fertilisation, the DNA contained within sperm and egg is combined to provide the full complement of genetic information that defines a unique human being. While the process of meiosis appears conceptually simple, it is in fact a complicated process that can frequently go wrong, resulting in either sperm or egg with the incorrect number of chromosomes, or in no germ cell being produced at all, causing miscarriage and infertility. It may also result in children being born with genetic diseases such as Down's syndrome.At the heart of meiosis is the process of genetic exchange between pairs of matching chromosomes. In order to be able to align with each other and exchange genetic material, each pair of matching chromosomes needs to be organised in a specific three-dimensional shape which is unique to meiosis. Previous research has shown that a large protein structure known as the synaptonemal complex (SC) is essential for this, by working as a molecular scaffold that holds chromosomes together in the correct way for the exchange of DNA to take place. Although the importance of the SC in meiosis has been known for a long time, we still know little regarding how the SC is constructed and how it functions. We plan to discover how the SC carries out its crucial function in meiosis by studying its complex molecular structure. Our specific aim is to work out exactly how the SC determines the shape of each matching chromosome, folding its DNA into the required three-dimensional structure necessary for the steps of pairing, genetic exchange and eventual separation. We will achieve this by producing a molecular picture at atomic resolution of the protein building blocks of the SC, which will show how they interact with the DNA and with each other, in order to build the correct molecular framework for genetic exchange to occur. Our research into the molecular structure of the SC will help us understand its important role in meiosis and to explain how defects in its assembly can lead to infertility, miscarriage and genetic disease. In addition, our work will improve our knowledge of the different ways in which human cells handle large chromosomal DNA molecules. This information is important as incorrect sorting of our chromosomes during cellular proliferation, caused by defective packaging of the DNA, can lead to unwanted alterations in the genome and to disease such as cancer.