Uncovering mechanisms controlling chromosome-specific behaviors during meiosis

项目摘要 减数分裂是一个严格控制的过程，在此过程中，二倍体基因组必须分离成单倍体 配子（即卵子或精子）。遗传不正确的染色体数目导致生育能力 出生缺陷。然而，染色体错误分离的原因并不总是保守的 染色体之间的差异和染色体间差异的原因仍然是未知的。一个关键 贡献者似乎是完全失去交叉或异常交叉放置。 黑腹果蝇是一个强大的模型，以更好地阐明染色体的调控- 异交及其对染色体分离的影响。在大多数情况下， 破坏交换在整个基因组中均匀地进行，使得很难理解 发生染色体特异性缺陷。然而，最近发现的一组突变体在部分损失- 功能联会复合体突变体在配对和重组中表现出实质上不同的缺陷 在X染色体和常染色体上。联会复合体是一种保守的减数分裂结构 它将同源染色体结合在一起，并且是交换发生所必需的。很长的- 本项目的长期目标是研究联会复合体如何调控染色体， 分离所必需的特殊重组和减数分裂行为。这项工作将调查1） 联会复合体在调节重组景观中的作用; 2） 染色体结构对减数分裂行为的重要性。此外，该项目将 建立一个新的工具包来分析单个染色体。总体而言，该项目将提供见解 交叉位置的调节和减数分裂染色体生物学。通过研究 单个染色体行为和联会复合体在重组中的重要性， 实质性的进展可以在理解生物学的发展基础上， 非整倍性

Project Summary Meiosis is a tightly controlled process during which the diploid genome must segregate into haploid gametes (i.e. eggs or sperm). Inheritance of the incorrect number of chromosomes causes fertility and birth defects. However, the causes of chromosome missegregation are not always conserved between chromosomes and the reasons for inter-chromosomal differences are still unknown. One key contributor appears to be either a complete loss of crossing over or abnormal crossover placement. Drosophila melanogaster is a powerful model to better elucidate the regulation of chromosome- specific crossing over and the effects on chromosome segregation. In most cases, mutants that disrupt crossing over do so uniformly across the genome making it difficult to understand how chromosome-specific defects occur. However, a recently identified set of mutants in a partial loss-of- function synaptonemal complex mutant exhibit substantially different defects in pairing and recombination on the X chromosome and the autosomes. The synaptonemal complex is a conserved meiotic structure that holds homologous chromosomes together and is necessary for crossing over to occur. The long- term goal of this project is to investigate how the synaptonemal complex regulates chromosome- specific recombination and meiotic behaviors necessary for segregation. This work will investigate 1) the role of the synaptonemal complex in regulating the recombination landscape and 2) the importance of chromosome structure informing meiotic behaviors. Furthermore, this project will establish a new toolkit for analyzing individual chromosomes. Overall, this project will provide insights into both the regulation of crossover location and meiotic chromosome biology. By studying the importance of individual chromosome behaviors and the synaptonemal complex in recombination, substantial advances can be made in understand the biology underlying the development of aneuploidies.