CAREER: Meiotic double strand break repair on sex chromosomes

职业：性染色体减数分裂双链断裂修复

• 批准号: 1943283
• 负责人: Michael White
• 金额: $ 105万
• 依托单位: University of Georgia Research Foundation Inc
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-12-15 至 2024-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1943283&HistoricalAwards=false
• 关键词: CAREER; Meiotic; double; strand; break

DNA double strand breaks occur throughout the genome during meiosis and must be properly repaired to ensure overall genome stability. This process is challenging on sex chromosomes (i.e., X and Y) because there is limited sequence shared by the two chromosomes available for repair. A clear understanding of how double strand breaks are resolved on these chromosomes is important, as it may have a role in maintaining essential gene function on an otherwise degenerating Y chromosome. In addition, errors in the process have been linked to several disorders, including sterility and sex reversal. This project will identify how double strand breaks are localized and repaired on X and Y chromosomes. It will also provide extensive training in research, teaching, and mentoring to junior scientists at all levels. Local secondary education teachers will also be recruited to develop inquiry-based curricula focused on sex chromosome biology. Finally, this project will enable a program at University of Georgia that supports undergraduate attendance at the annual Southeastern Population, Ecology, and Evolutionary Genetics Conference.The overall goals of this project are to use the young sex chromosomes of the threespine stickleback fish to (a) understand how double strand break initiation and repair occurs, and (b) clarify how these processes influence the preservation of gene function on the Y chromosome. An array of comparative and functional genomics, gene editing and cytogenetics approaches will be employed to address the specific aims. Aim 1 will determine how double strand breaks are localized and whether breaks are associated with sex-chromosome-specific changes in chromatin features. Aim 2 will identify the preferential repair templates for double strand breaks across sex chromosomes. Aim 3 will determine whether genes subject to non-crossover gene conversion on sex chromosomes have essential functions. The results of this project will be broadly applicable across species, as meiotic recombination is highly conserved across the tree of life and utilizes the same proteins to regulate double strand break initiation and repair on sex chromosomes and autosomes alike.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

DNA双链断裂在减数分裂期间发生在整个基因组中，并且必须适当修复以确保整体基因组稳定性。这一过程对性染色体具有挑战性（即，X和Y），因为两条染色体可用于修复的序列有限。清楚地了解这些染色体上的双链断裂是如何解决的是很重要的，因为它可能在维持退化Y染色体上的基本基因功能方面发挥作用。此外，这一过程中的错误与几种疾病有关，包括不育和性逆转。这个项目将确定如何双链断裂定位和修复的X和Y染色体。它还将为各级青年科学家提供广泛的研究、教学和指导培训。还将招聘当地中学教师，以制定以性染色体生物学为重点的探究式课程。最后，这个项目将使格鲁吉亚大学的一个项目能够支持本科生参加一年一度的东南部人口、生态学和进化遗传学会议。这个项目的总体目标是利用三棘鱼的年轻性染色体来（a）了解双链断裂起始和修复是如何发生的，和（B）阐明这些过程如何影响Y染色体上基因功能的保存。将采用一系列比较和功能基因组学、基因编辑和细胞遗传学方法来实现具体目标。目的1将确定双链断裂是如何定位的，以及断裂是否与染色质特征的性染色体特异性变化相关。目的二是寻找性染色体双链断裂的优先修复模板。目标3将确定性染色体上的非交换基因转换的基因是否具有基本功能。该项目的结果将广泛适用于不同物种，因为减数分裂重组在生命树中高度保守，并利用相同的蛋白质来调节性染色体和常染色体上双链断裂的启动和修复。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Meiotic pairing and double-strand break formation along the heteromorphic threespine stickleback sex chromosomes

异形三刺刺鱼性染色体减数分裂配对和双链断裂形成

• DOI: 10.1007/s10577-022-09699-0
• 发表时间: 2022
• 期刊: Chromosome Research
• 影响因子: 2.6
• 作者: Nath, Shivangi;Welch, Lucille A.;Flanagan, Mary K.;White, Michael A.
• 通讯作者: White, Michael A.

Assembly of the threespine stickleback Y chromosome reveals convergent signatures of sex chromosome evolution

• DOI: 10.1186/s13059-020-02097-x
• 发表时间: 2020-07-19
• 期刊: GENOME BIOLOGY
• 影响因子: 12.3
• 作者: Peichel, Catherine L.;McCann, Shaugnessy R.;White, Michael A.
• 通讯作者: White, Michael A.