从体性子宫组织中得到的DNA损伤信号通过激活的DAF-16来阻止子宫生殖
Gautam Chandra Sarkar1, Umanshi Rautela1, Anita Goyala1
1Molecular Aging Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
概括
当胰岛素信号低时,体内DNA损伤会扰乱生殖线的发展. FOXO/DAF-16通路强制执行严格的质量控制,停止生殖过程以确保后代的健康.
科学领域:
- 细胞和发育生物学
- 遗传学和基因组学 遗传学和基因组学
- 生殖生物学 生殖生物学
背景情况:
- 生殖线的完整性对于后代的健康至关重要.
- DNA损伤反应 (DDR) 保护胚胎细胞免受基因毒性压力.
- 在生殖线中,细胞非自主质量控制机制的理解较少.
研究的目的:
- 为了研究体质DNA损伤如何影响生殖线质量非自主.
- 阐明胰岛素/IGF-1信号传导 (IIS) 和FOXO/DAF-16在这个过程中的作用.
- 确定将体质DDR与生殖系调节联系起来的分子通路.
主要方法:
- 使用了模型生物Caenorhabditis elegans.
- 在特定组织 (子宫) 中操纵了DNA损伤反应 (DDR) 和胰岛素/IGF-1信号传导 (IIS).
- 分析了 oogenesis 的进展,生殖细胞质量和基因表达 (FOXO/DAF-16,ERK/MPK-1).
主要成果:
- 在低IIS期间子宫中DDR的干扰会在帕奇阶段停止 oogenesis.
- 这种捕获取决于转录因子FOXO/DAF-16.
- 在低IIS条件下,FOXO/DAF-16功能的丧失导致低质量的卵细胞的产生.
- 激活的FOXO/DAF-16抑制了ERK/MPK-1信号传递,促进了生殖线的停止.
结论:
- 激活的FOXO/DAF-16充当监控机制,在低 IIS 期间感知 DDR 干扰.
- 这一途径对生殖过程施加了严格的质量控制,确保了生殖细胞的质量和后代的健康.
- 鉴定了FOXO/DAF-16在调解非自主生殖系质量控制中的新型作用,以应对体质DNA损伤.
相关概念视频
Oogenesis
63.8K
In human women, oogenesis produces one mature egg cell or ovum for every precursor cell that enters meiosis. This process differs in two unique ways from the equivalent procedure of spermatogenesis in males. First, meiotic divisions during oogenesis are asymmetric, meaning that a large oocyte (containing most of the cytoplasm) and minor polar body are produced as a result of meiosis I, and again following meiosis II. Since only oocytes will go on to form embryos if fertilized, this unequal...
63.8K
DNA Damage can Stall the Cell Cycle
9.2K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.2K
DNA Damage Can Stall the Cell Cycle
2.6K
2.6K
Nondisjunction
3.9K
Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate correctly and move to the opposite poles of the cells. This produces daughter cells with abnormal chromosome numbers. Nondisjunction is common during anaphase I or anaphase II of meiosis. Mutations in synaptonemal complex proteins that attach homologous chromosomes increase the chances of nondisjunction in anaphase I of meiosis I. In contrast, mutations in topoisomerases and condensins that hold...
3.9K
Mutations
38.3K
Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
38.3K
Nucleotide Excision Repair
3.6K
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
3.6K


