Functional Characterisation of APLF; A Novel Human Protein Involved in the Cellular Response to Chromosomal DNA Strand Breaks

APLF 的功能表征；

• 批准号: BB/F013930/1
• 负责人: Keith Caldecott
• 金额: $ 51.52万
• 依托单位: University of Sussex
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF013930%2F1
• 关键词: Functional; Characterisation; APLF; Novel; Human

The DNA in our cells is damaged more than 10,000 times per cell per day. If not repaired properly, this damage can result in genetic mutations and/or cell death. Consequently, cells have evolved a number of sophisticated biochemical mechanisms by which damaged DNA is rapidly detected and repaired. Recently, my group identified a completely novel human DNA repair protein that we denoted Aprataxin and PNK-Like Factor, or APLF. We have discovered that APLF is important for ensuring that breaks in one or both strands of DNA are repaired as fast as possible. Here, we plan to characterise in detail the importance of APLF for genetic integrity and genetic stability in living cells and in animals. In addition, we will identify the biochemical function of APLF and integrate this role into our model for how DNA strand breaks are repaired in human cells.

我们细胞中的DNA每天每个细胞被破坏超过10，000次。如果不正确修复，这种损伤可能导致基因突变和/或细胞死亡。因此，细胞已经进化出许多复杂的生化机制，通过这些机制，受损的DNA被迅速检测和修复。最近，我的团队发现了一种全新的人类DNA修复蛋白，我们将其命名为Aprataxin和PNK样因子，或APLF。我们发现APLF对于确保DNA的一条或两条链的断裂尽快修复非常重要。在这里，我们计划详细阐述APLF对活细胞和动物的遗传完整性和遗传稳定性的重要性。此外，我们将确定APLF的生化功能，并将此作用整合到我们的模型中，以了解DNA链断裂如何在人类细胞中修复。

项目成果

Versatility in phospho-dependent molecular recognition of the XRCC1 and XRCC4 DNA-damage scaffolds by aprataxin-family FHA domains.

Aprataxin-Fha域对XRCC1和XRCC4 DNA破坏支架的磷酸依赖性分子识别的多功能性。

• DOI: 10.1016/j.dnarep.2015.10.002
• 发表时间: 2015-11
• 期刊: DNA repair
• 影响因子: 3.8
• 作者: Cherry AL;Nott TJ;Kelly G;Rulten SL;Caldecott KW;Smerdon SJ
• 通讯作者: Smerdon SJ