Apoptosis in recombination-deficient meiocytes

重组缺陷性母细胞中的细胞凋亡

• 批准号: 7243435
• 负责人: Francesca Cole
• 金额: $ 5.04万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7243435
• 关键词: Apoptosis; Apoptotic; Cell Cycle; Cell Death; Cells; Chromosome Segregation; Chromosome Structures; Chromosomes; Defect; Development; Elements; Ensure; Generations; Genes; Genetic; Genetic Recombination; Germ Cells; Haploidy; Injury; Meiosis; Meiotic Recombination; Metabolism; Molecular; Monitor; Oogenesis; Organism; Pathway interactions; Ploidies; Signal Transduction; Spermatogenesis; Testing; Work; cytotoxic; homologous recombination; response; sex; sexual dimorphism

DESCRIPTION (provided by applicant): Meiotic recombination is required to align homologous chromosomes for segregation during the first meiotic division. Meiocytes monitor key steps in meiosis and defective progression results in activation of meiotic checkpoints that induce programmed cell death. Recent studies have identified elements that control programmed cell death in the germline during the course of normal development as well as in response to cytotoxic injury. But less is known about the genetic control of apoptosis in response to errors in meiotic chromosome metabolism. Preliminary work suggests that meiocytes have both DMA damage-dependent and -independent meiotic checkpoints. Intriguingly, these checkpoints are differentially utilized during spermatogenesis and oogenesis. The work detailed in this proposal seeks to answer these specific aims: 1) to determine which apoptotic signaling cascades are activated as a result of meiotic recombination errors in spermatogenesis and oogenesis; 2) to genetically test whether specific pro-apoptotic pathway genes are required for recombination-defective meiocyte cell death and to determine whether the observed sexual dimorphism in cell cycle responses is a consequence of differential use of these genes.

描述（由申请人提供）：需要减数分裂重组才能使第一个减数分裂部门的同源染色体对齐。细胞细胞监测减数分裂和进展不良的关键步骤导致诱导程序性细胞死亡的减数分裂检查点的激活。最近的研究已经确定了在正常发育过程中以及对细胞毒性损伤的响应过程中控制种系中编程细胞死亡的元素。但是，对减数分裂染色体代谢的错误的凋亡的遗传控制知之甚少。初步工作表明，量量细胞具有DMA损伤依赖性和非依赖性减数分裂检查点。有趣的是，这些检查点在精子发生和卵子发生过程中被差异化。该提案中详细介绍的工作旨在回答以下特定目的：1）确定由于精子发生和卵子发生中的减数分裂重组误差而激活了哪些凋亡信号级联； 2）在遗传上测试重组缺陷型肠细胞死亡是否需要特定的促凋亡途径基因，并确定细胞周期反应中观察到的性二态性是否是对这些基因不同使用的结果。