Processing of Spo11-induced covalent protein-linked DNA double-strand breaks in meiosis

我们体内的每个细胞都含有染色体，这些染色体储存着我们从父母的配子细胞（卵子和精子）那里继承来的遗传信息。在我们自己的配子细胞的生产过程中，这些遗传信息必须被仔细地复制，精确地减半，并准确地储存。这个过程中的错误会导致不育，或者在极少数情况下导致后代遗传异常。丢弃一半的遗传信息是一个冒险的过程，但却是必要的。只有将卵子和精子中的遗传信息结合起来，才会孕育出具有正确数量染色体信息的人类。我们的研究将集中在理解在配子形成过程中发生在我们DNA中的分子反应，重点是理解一种进化上保守的蛋白质的基本作用，称为Spo11。在配子细胞的形成过程中，Spo11在我们的染色体上造成了多次断裂，实际上在许多地方与DNA紧密结合。从DNA中去除Spo11是至关重要的，但直到最近，人们对这一过程知之甚少。我们的研究将调查细胞用来去除Spo11的方法，旨在更多地了解这一重要过程的控制。我们将在贝克？酵母，一种简单的有性繁殖模式生物。由于简单模式生物和人类具有相同的基本过程，模式生物为开展与人类健康有关的基础研究提供了一种合乎道德和经济的方式。一旦从模式生物研究中获得基本的了解，结果将应用于更高级的人类健康研究。我们将通过在同行评议的期刊上发表论文、在科学会议上发表演讲、通过开放日、学校访问和在布莱顿？这是一年一度的科学周。

Each cell in our body contains chromosomes that store the genetic information that we inherited from the gamete cells (egg and sperm) of our parents. During the production of our own gamete cells, this genetic information must be carefully copied, precisely halved, and accurately deposited. Errors in this process lead to infertility, or in rare cases to offspring with genetic abnormalities. Discarding half of all the genetic information is a risky procedure, but an essential one. Only by combining the genetic information contained in eggs and sperm are human beings conceived with the correct amount of chromosomal information. Our research will concentrate on understanding the molecular reactions that take place in our DNA during gamete formation, with emphasis on understanding the essential role of an evolutionarily conserved protein, referred to as Spo11. During the creation of gamete cells, Spo11 creates multiple breaks in our chromosomes, and in fact becomes tightly bound to the DNA in many places. It is essential that Spo11 be removed from the DNA, but until recently this process was poorly understood. Our research will investigate the methods that cells use to remove Spo11, aiming to learn much more about the control of this essential process. We will perform the studies in baker?s yeast, a simple sexually reproducing model organism. Because simple model organisms and humans share the same fundamental processes, model organisms provide an ethical and economical way to perform basic research that is relevant to human health. Once a basic understanding is obtained from the model organism study, the results will be applied to more advanced human health studies.We will convey our research findings by publication in peer-reviewed journals, presentations at scientific meetings, and by participation with the public and the media via open days, school visits, and at Brighton?s annual Science Week.