Biochemistry and Regulation of Mammalian DNA Repair

哺乳动物 DNA 修复的生物化学和调控

• 批准号: MC_UU_00001/3
• 负责人: Grigory Dianov
• 金额: $ 44.47万
• 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%2F3
• 关键词: Biochemistry; Regulation; Mammalian; DNA; Repair

DNA base excision repair (BER) is the principal DNA repair system in cancer cells, which counteracts the killing effect of major cancer treatments e.g., chemotherapy and ionizing radiation. Changes in BER capacity most probably are responsible for the efficiency of cancer treatment, as many cancers have an altered amount of BER proteins. Although BER proteins have been studied in detail, the mechanisms involved in BER coordination, their regulation and consequences of their malfunction are unclear. This gap in knowledge is impeding the discovery of new cancer therapy targets and the development of novel cancer treatment strategies. The objective of the Biochemistry Group is to identify new mechanisms and proteins that are responsible for the coordination and regulation of the BER pathway in human cells and to understand their role in processing endogenous and radiation induced DNA lesions, with a final goal to improve the efficiency of cancer therapy.

DNA碱基切除修复（BER）是癌细胞中的主要DNA修复系统，其抵消主要癌症治疗的杀伤作用，化疗和电离辐射。BER容量的变化很可能是癌症治疗效率的原因，因为许多癌症的BER蛋白量发生了变化。虽然BER蛋白已被详细研究，但BER协调，其调节和其故障的后果所涉及的机制尚不清楚。这种知识上的差距阻碍了新的癌症治疗靶点的发现和新的癌症治疗策略的开发。生物化学组的目标是确定负责协调和调节人类细胞中BER途径的新机制和蛋白质，并了解它们在处理内源性和辐射诱导的DNA损伤中的作用，最终目标是提高癌症治疗的效率。

项目成果

Interplay between base excision repair protein XRCC1 and ALDH2 predicts overall survival in lung and liver cancer patients.

• DOI: 10.1007/s13402-018-0390-8
• 发表时间: 2018-10
• 期刊: Cellular oncology (Dordrecht, Netherlands)
• 作者: Chen X;Legrand AJ;Cunniffe S;Hume S;Poletto M;Vaz B;Ramadan K;Yao D;Dianov GL
• 通讯作者: Dianov GL

A unified model for the G1/S cell cycle transition.

• DOI: 10.1093/nar/gkaa1002
• 发表时间: 2020-12-16
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Hume S;Dianov GL;Ramadan K
• 通讯作者: Ramadan K

The NUCKS1-SKP2-p21/p27 axis controls S phase entry.

• DOI: 10.1038/s41467-021-27124-8
• 发表时间: 2021-11-29
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Hume S;Grou CP;Lascaux P;D'Angiolella V;Legrand AJ;Ramadan K;Dianov GL
• 通讯作者: Dianov GL