Elucidation of mechanisms ensuring optimal double-strand break number in meiotic cells
阐明确保减数分裂细胞中最佳双链断裂数的机制
基本信息
- 批准号:21H02400
- 负责人:
- 金额:$ 11.07万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (B)
- 财政年份:2021
- 资助国家:日本
- 起止时间:2021-04-01 至 2024-03-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
We have continued to address the mechanisms of meiotic double-strand break (DSB) control by phosphoregulation of the protein DSB-1 in this fiscal year.We found that mutating a single serine residue in DSB-1, S186, to alanine, leads to hyperactive DSB formation, even in the absence of the protein DSB-2. Loss of DSB-2 norally leads to high embryonic inviability due to loss of DSBs. Since loss of DSB-2 can be rescued so easily, we reasoned that it might be required for long-term genome stability. We therefore have performed whole-genome long-read sequencing on DSB-1 non-phosphorylatable mutant lines that have been experiencing high DSB levels for over 50 generations. While analysis of this sequence information is still in progress, individual mutant animals have been isolated with spontaneous mutations and spontaneous tetraploidization. Since spontaneous tetraploidization is never observed in wild-type animals, it is plausible that the genome has become less stable in the non-phosphorylatable DSB-1 mutant animals.Our attempts to directly demonstrate phosphorylation of DSB-1 by phosphospecific antibody production or mass spectrometry have not yet been successful; however, we have now completed construction of a FLAG-tagged DSB-1 allele with full viability that is very clean on a western blot; this reagent should greatly aid in our further efforts to characterize DSB-1.
本年度继续研究通过DSB-1蛋白的磷酸化调节来控制减数分裂双链断裂(DSB)的机制,发现即使在DSB-2蛋白缺失的情况下,将DSB-1中的一个丝氨酸残基S186突变为丙氨酸,也会导致DSB的过度形成。DSB-2的丢失通常会导致由于DSB丢失而导致的高胚胎不存活率。由于DSB-2的丢失可以很容易地被挽救,我们推断它可能是长期基因组稳定所必需的。因此,我们对DSB-1不可磷酸化突变株系进行了全基因组长读段测序,这些突变株系经历了超过50代的高DSB水平。虽然对该序列信息的分析仍在进行中,但已分离出具有自发突变和自发四倍化的个体突变动物。由于在野生型动物中从未观察到自发的四倍化,所以在不可磷酸化的DSB-1突变动物中基因组变得不太稳定是合理的。然而,我们现在已经完成了FLAG标记DSB-1等位基因的构建,其具有完全的活力,在蛋白质印迹上非常干净;该试剂将极大地帮助我们进一步表征DSB-1。
项目成果
期刊论文数量(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Nematode chromosomes.
线虫染色体。
- DOI:10.1093/genetics/iyac014
- 发表时间:2022-05-05
- 期刊:
- 影响因子:3.3
- 作者:Carlton, Peter M.;Davis, Richard E.;Ahmed, Shawn
- 通讯作者:Ahmed, Shawn
Phosphoregulation of DSB initiation
DSB 引发的磷酸调节
- DOI:
- 发表时间:2022
- 期刊:
- 影响因子:0
- 作者:Noda Taichi;Blaha Andreas;Fujihara Yoshitaka;Gert Krista R.;Emori Chihiro;Deneke Victoria E.;Oura Seiya;Panser Karin;Lu Yonggang;Berent Sara;Kodani Mayo;Cabrera-Quio Luis Enrique;Pauli Andrea;Ikawa Masahito;Peter CARLTON
- 通讯作者:Peter CARLTON
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Carlton Peter其他文献
5-hydroxymethylcytosine marks sites of DNA damage and promotes genome integrity
5-羟甲基胞嘧啶标记 DNA 损伤位点并促进基因组完整性
- DOI:
- 发表时间:
2016 - 期刊:
- 影响因子:0
- 作者:
Carlton Peter - 通讯作者:
Carlton Peter
Carlton Peter的其他文献
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{{ truncateString('Carlton Peter', 18)}}的其他基金
減数分裂前期におけるDNA切断の場を形成する分子メカニズムの解明
阐明减数分裂前期形成 DNA 切割位点的分子机制
- 批准号:
24K01955 - 财政年份:2024
- 资助金额:
$ 11.07万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Elucidating the mechanisms of chromosome length sensing by the synaptonemal complex
阐明联会复合体感知染色体长度的机制
- 批准号:
22K19272 - 财政年份:2022
- 资助金额:
$ 11.07万 - 项目类别:
Grant-in-Aid for Challenging Research (Exploratory)
Mechanisms that promote the correct completion of meiosis by breaking symmetry of chromosomes
通过打破染色体对称性促进减数分裂正确完成的机制
- 批准号:
18H02373 - 财政年份:2018
- 资助金额:
$ 11.07万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
卵母細胞における染色体ダイナミクス制御と母体の加齢効果
卵母细胞染色体动态的控制和母亲衰老的影响
- 批准号:
16F16088 - 财政年份:2016
- 资助金额:
$ 11.07万 - 项目类别:
Grant-in-Aid for JSPS Fellows
Investigating phosphoregulation of meiotic recombination using superresolution microscopy
使用超分辨率显微镜研究减数分裂重组的磷酸调节
- 批准号:
15H04328 - 财政年份:2015
- 资助金额:
$ 11.07万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
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Discovery and validation of avermectin resistance loci in free-living and parasitic nematodes
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線虫の減数分裂前期において染色体の動的なふるまいを制御する分子機構
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WormBase: a core data resource for C elegans and other nematodes
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8325682 - 财政年份:2000
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