Role and regulation of cyclin F in the cellular responses to ionizing radiation (IR).

细胞周期蛋白 F 在细胞电离辐射 (IR) 反应中的作用和调节。

• 批准号: MC_UU_00001/7
• 负责人: Vincenzo D'Angiolella
• 金额: $ 225.92万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Intramural
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MC_UU_00001%2F7
• 关键词: Role; regulation; cyclin; cellular; responses

Each cell in our body duplicates itself by copying its main information hub: the DNA. To ensure that the information contained in the DNA is not altered during the process of cell division, cells have evolved checkpoints that monitor the correct execution of DNA replication. Studies from the laboratory of Dr Vincenzo D’Angiolella have revealed how the balance of the building blocks composing the DNA molecule is maintained in the cell cycle and how this is coordinated with the execution of checkpoints. The laboratory discovered that the organized synthesis and removal of the enzymes responsible for the production of the building blocks is crucial to ensure the fidelity of DNA replication and cell survival.A characteristic feature cancer cells is the loss of checkpoints. The lack of checkpoint control provides cancer cells with a proliferative advantage at the cost of increased susceptibility to agents damaging the DNA molecule. This is exploited in cancer therapy through the use of radiation therapy.Future studies will focus on elucidating the function of genes that modulate the checkpoint responses of cancer cells to radiation therapy. These studies will reveal novel potential weakness to increase the efficacy of radiation therapy for cancer treatment.

我们身体中的每个细胞都通过复制其主要信息中心：DNA来复制自己。为了确保DNA中包含的信息在细胞分裂过程中不被改变，细胞已经进化出了检查点来监控DNA复制的正确执行。D'Angiolella博士实验室的研究揭示了构成DNA分子的构建块的平衡如何在细胞周期中维持，以及如何与检查点的执行协调。该实验室发现，负责生产积木的酶的有组织的合成和去除对于确保DNA复制的保真度和细胞存活至关重要。癌细胞的一个特征是检查点的丢失。缺乏检查点控制为癌细胞提供了增殖优势，但代价是对损伤DNA分子的试剂的易感性增加。未来的研究将集中在阐明调节癌细胞对放射治疗的检查点反应的基因的功能上。这些研究将揭示新的潜在弱点，以提高放射治疗癌症的疗效。

项目成果

Two paths to let the replisome go.

• DOI: 10.1038/cdd.2017.75
• 发表时间: 2017-07
• 期刊: Cell death and differentiation
• 影响因子: 12.4
• 作者: D'Angiolella V;Guardavaccaro D
• 通讯作者: Guardavaccaro D

FBXL13 directs the proteolysis of CEP192 to regulate centrosome homeostasis and cell migration

• DOI: 10.15252/embr.201744799
• 发表时间: 2018-03-01
• 期刊: EMBO REPORTS
• 影响因子: 7.7
• 作者: Fung, Ella;Richter, Carmen;D'Angiolella, Vincenzo
• 通讯作者: D'Angiolella, Vincenzo

Cyclin F-Chk1 synthetic lethality mediated by E2F1 degradation

E2F1 降解介导的 Cyclin F-Chk1 合成致死率

• DOI: 10.1101/509810
• 发表时间: 2019
• 作者: Burdova K

Sequence and structural variations determining the recruitment of WNK kinases to the KLHL3 E3 ligase.

• DOI: 10.1042/bcj20220019
• 发表时间: 2022-03-18
• 期刊: The Biochemical journal

E2F1: Cause and Consequence of DNA Replication Stress.

• DOI: 10.3389/fmolb.2020.599332
• 发表时间: 2020
• 期刊: Frontiers in molecular biosciences
• 影响因子: 5
• 作者: Fouad S;Hauton D;D'Angiolella V
• 通讯作者: D'Angiolella V