Chromosome Breaks and the DNA Damage Response in Transcribed Genes
转录基因中的染色体断裂和 DNA 损伤反应
基本信息
- 批准号:MR/X006778/2
- 负责人:
- 金额:$ 220.28万
- 依托单位:
- 依托单位国家:英国
- 项目类别:Research Grant
- 财政年份:2023
- 资助国家:英国
- 起止时间:2023 至 无数据
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
DNA double-strand breaks (DSBs) can arise through normal DNA metabolism or through exposure to DNA damaging agents such as ionizing radiation (IR), and can lead to breaks in our chromosomes which store our genetic information. These lesions are normally repaired by one of two DSB repair pathways termed non-homologous end joining (NHEJ), or homologous recombination (HR) repair pathways. DSB repair is important as failure to repair such lesions can cause cell death, and their misrepair can trigger chromosomal rearrangements, which can lead to cancer. While considerable advances have been made in our understanding of DSB repair, how it occurs in the context of transcription, in which the genetic material within genes is copied into messenger RNA to facilitate protein production, is unclear. The aim of the proposed research is to understand how cells respond to chromosome breaks within transcribed genes and facilitate their accurate repair by homologous recombination. In particular, we will explore the roles of chromatin (structures in which DNA is wrapped up in) and the transcription machinery (which copies DNA into messenger RNA) in coordinating these responses. The proposed research will provide mechanistic insights into DSB detection and repair within transcribed genes, and further, how defects in these processes can be exploited to target particular cancers.
DNA双链断裂(DSB)可以通过正常的DNA代谢或通过暴露于DNA损伤剂如电离辐射(IR)而产生,并可能导致我们的染色体断裂,这些染色体存储我们的遗传信息。这些损伤通常通过称为非同源末端连接(NHEJ)或同源重组(HR)修复途径的两种DSB修复途径之一修复。DSB修复是重要的,因为不能修复这些病变可能导致细胞死亡,并且它们的错误修复可能引发染色体重排,这可能导致癌症。虽然我们对DSB修复的理解已经取得了相当大的进展,但它如何在转录的背景下发生,其中基因内的遗传物质被复制到信使RNA中以促进蛋白质的产生,目前尚不清楚。这项研究的目的是了解细胞如何对转录基因内的染色体断裂做出反应,并通过同源重组促进其准确修复。特别是,我们将探讨染色质(DNA包裹的结构)和转录机制(将DNA复制成信使RNA)在协调这些反应中的作用。这项研究将为转录基因内的DSB检测和修复提供机制性见解,以及如何利用这些过程中的缺陷来靶向特定癌症。
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Using canavanine resistance to measure mutation rates in Schizosaccharomyces pombe.
- DOI:10.1371/journal.pone.0271016
- 发表时间:2023
- 期刊:
- 影响因子:3.7
- 作者:Pai, Chen-Chun;Heitzer, Ellen C.;Bertrand, Sibyl E.;Toumazou, Sophia;Humphrey, Timothy C.;Kearsey, Stephen E.
- 通讯作者:Kearsey, Stephen E.
Homologous recombination suppresses transgenerational DNA end resection and chromosomal instability in fission yeast.
- DOI:10.1093/nar/gkad160
- 发表时间:2023-04-24
- 期刊:
- 影响因子:14.9
- 作者:Pai, Chen-Chun;Durley, Samuel C.;Cheng, Wei-Chen;Chiang, Nien-Yi;Peters, Jennifer;Kasparek, Torben;Blaikley, Elizabeth;Wee, Boon-Yu;Walker, Carol;Kearsey, Stephen E.;Buffa, Francesca;Murray, Johanne M.;Humphrey, Timothy C.
- 通讯作者:Humphrey, Timothy C.
A role for SETD2 loss in tumorigenesis through DNA methylation dysregulation.
- DOI:10.1186/s12885-023-11162-0
- 发表时间:2023-08-01
- 期刊:
- 影响因子:3.8
- 作者:Javaid, Hira;Barberis, Alessandro;Chervova, Olga;Nassiri, Isar;Voloshin, Vitaly;Sato, Yusuke;Ogawa, Seishi;Fairfax, Benjamin;Buffa, Francesca;Humphrey, Timothy C. C.
- 通讯作者:Humphrey, Timothy C. C.
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Timothy Humphrey其他文献
Timothy Humphrey的其他文献
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{{ truncateString('Timothy Humphrey', 18)}}的其他基金
Chromosome Breaks and the DNA Damage Response in Transcribed Genes
转录基因中的染色体断裂和 DNA 损伤反应
- 批准号:
MR/X006778/1 - 财政年份:2022
- 资助金额:
$ 220.28万 - 项目类别:
Research Grant
Understanding how genome stability is maintained in response to chromosomal breaks.
了解如何在应对染色体断裂时维持基因组稳定性。
- 批准号:
MC_UU_00001/4 - 财政年份:2017
- 资助金额:
$ 220.28万 - 项目类别:
Intramural
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Chromosome Breaks and the DNA Damage Response in Transcribed Genes
转录基因中的染色体断裂和 DNA 损伤反应
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- 资助金额:
$ 220.28万 - 项目类别:
Research Grant