The cellular response to complex DNA damage induced by ionising radiation

细胞对电离辐射引起的复杂 DNA 损伤的反应

• 批准号: MR/M000354/1
• 负责人: Jason Luke Parsons
• 金额: $ 45.43万
• 依托单位: University of Liverpool
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FM000354%2F1
• 关键词: cellular; response; complex; DNA; damage

DNA in our chromosomes encodes genetic information that is essential to life. However, damage to our DNA by ionising radiation from the environment is a constant daily occurrence and DNA damage accumulation is thought to be involved in the development of ageing, neurodegenerative diseases and cancer. To combat this, our cells usually contain efficient DNA repair mechanisms that act to prevent the development of these human diseases. Conversely radiotherapy, in the form of ionising radiation, is also still the most effective treatment for killing cancer cells, although it's effectiveness is variable in different cancers and side effects can be common. Despite this knowledge, complete information on how our cells repair DNA damage induced by ionising radiation in our chromosomes is still unclear and is the focus of the proposed research. This proposal is therefore essential for our understanding of the basic biological mechanisms our cells use to prevent DNA damage accumulation caused by ionising radiation, and thus act to stop the formation of human diseases. Furthermore, this proposal aims to provide leads to the development of new strategies in combination with radiotherapy, for the effective treatment of cancer.

我们染色体中的DNA编码对生命至关重要的遗传信息。然而，来自环境的电离辐射对我们的DNA的损伤是每天不断发生的，DNA损伤的积累被认为与衰老、神经退行性疾病和癌症的发展有关。为了解决这个问题，我们的细胞通常含有有效的DNA修复机制，可以防止这些人类疾病的发展。相反，电离辐射形式的放射治疗仍然是杀死癌细胞的最有效的治疗方法，尽管它的有效性在不同的癌症中是可变的，副作用可能是常见的。尽管有这些知识，关于我们的细胞如何修复染色体中电离辐射引起的DNA损伤的完整信息仍然不清楚，这是拟议研究的重点。因此，这一提议对于我们理解细胞用于防止电离辐射引起的DNA损伤积累的基本生物学机制至关重要，从而采取行动阻止人类疾病的形成。此外，该提案旨在为开发与放射治疗相结合的新策略提供线索，以有效治疗癌症。

项目成果

USP9X Inhibition Enhances Radiosensitisation of Head and Neck Cancer Cells in Response to High-LET Radiation by Destabilising Centrosome Proteins

USP9X 抑制通过破坏中心体蛋白的稳定性来增强头颈癌细胞对高 LET 辐射的放射敏感性

• DOI: 10.3390/iecc2021-09211
• 发表时间: 2021
• 作者: Fabbrizi M

Cell death mechanisms in head and neck cancer cells in response to low and high-LET radiation

• DOI: 10.1017/erm.2021.31
• 发表时间: 2022-01-12
• 期刊: EXPERT REVIEWS IN MOLECULAR MEDICINE
• 影响因子: 6.2
• 作者: Fabbrizi, Maria Rita;Parsons, Jason L.
• 通讯作者: Parsons, Jason L.

Complex DNA Damage Induced by High Linear Energy Transfer Alpha-Particles and Protons Triggers a Specific Cellular DNA Damage Response.

• DOI: 10.1016/j.ijrobp.2017.11.012
• 发表时间: 2018-03-01
• 期刊: International journal of radiation oncology, biology, physics
• 作者: Carter RJ;Nickson CM;Thompson JM;Kacperek A;Hill MA;Parsons JL
• 通讯作者: Parsons JL

Ubiquitylation-dependent regulation of NEIL1 by Mule and TRIM26 is required for the cellular DNA damage response.

• DOI: 10.1093/nar/gkw959
• 发表时间: 2017-01-25
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Edmonds MJ;Carter RJ;Nickson CM;Williams SC;Parsons JL
• 通讯作者: Parsons JL

The Enzyme-Modified Neutral Comet (EMNC) Assay for Complex DNA Damage Detection.

• DOI: 10.3390/mps4010014
• 发表时间: 2021-02-16
• 期刊: Methods and protocols
• 影响因子: 2.4
• 作者: Fabbrizi MR;Hughes JR;Parsons JL
• 通讯作者: Parsons JL