Controlling chromosome structure in starved bacteria

控制饥饿细菌的染色体结构

• 批准号: BB/H010289/1
• 负责人: David Grainger
• 金额: $ 42.04万
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FH010289%2F1
• 关键词: Controlling; chromosome; structure; starved; bacteria

DNA can be envisaged as a long piece of string and, just like string, if not carefully wound, DNA becomes a tangled mess. This presents a problem for living organisms because they have to package their string of DNA within the confines of a small compartment (the cell). Cells have evolved numerous mechanisms to package DNA and, for more complicated organisms (for example humans and plants) we have a reasonably good understanding of how these mechanisms work. However, our understanding of chromosome folding in bacteria (such as the familiar organisms E. coli and Salmonella) is less well developed. In our work we propose to identify mechanisms used by bacteria to organise their DNA. In particular we will pay attention to DNA organisation in starved bacteria. This is important because, in starved bacteria, the DNA string is packaged much more tightly than normal. It is believed that this is a protection mechanism to ensure that DNA is not damaged in the harsh environments bacteria may encounter when not growing in optimal conditions. For example, E. coli transferred to a chopping board from contaminated meat would employ such protection mechanisms until it encountered a more favourable environment (i.e. the gut of you or I). Our study will focus on a protein called Curved DNA Binding Protein A (CbpA) that binds to the DNA and is produced by E. coli cells only when they are starved. Our goals are to determine, exactly how CbpA structures DNA, which parts of the DNA are associated with CbpA, and how CbpA activity is regulated. Because CbpA is also produced by bacteria related to E. coli, such as Salmonella, our findings should also be applicable to these organisms.

DNA可以被想象成一根长长的绳子，就像绳子一样，如果不小心缠绕，DNA就会变得一团糟。这给生物体带来了一个问题，因为它们必须在一个小隔间（细胞）的范围内包装它们的DNA链。细胞已经进化出许多包装DNA的机制，对于更复杂的生物体（例如人类和植物），我们对这些机制的工作原理有相当好的了解。然而，我们对细菌染色体折叠的理解（如熟悉的生物体E。大肠杆菌和沙门氏菌）的发展较不完善。在我们的工作中，我们建议确定细菌用来组织其DNA的机制。我们将特别关注饥饿细菌中的DNA组织。这一点很重要，因为在饥饿的细菌中，DNA串比正常情况下包装得更紧密。据信，这是一种保护机制，以确保DNA不会在细菌在最佳条件下生长时可能遇到的恶劣环境中受损。例如，E.从受污染肉类转移到砧板上的大肠杆菌会采用这种保护机制，直到它遇到更有利的环境（即你或我的肠道）。我们的研究将集中在一种称为弯曲DNA结合蛋白A（CbpA）的蛋白质上，该蛋白质与DNA结合，由E。大肠杆菌细胞只有在饥饿时才能存活。我们的目标是确定CbpA如何构建DNA，DNA的哪些部分与CbpA相关，以及CbpA活性如何调节。由于CbpA也是由与E.大肠杆菌，如沙门氏菌，我们的研究结果也应该适用于这些生物。

项目成果

E. coli Fis protein insulates the cbpA gene from uncontrolled transcription.

• DOI: 10.1371/journal.pgen.1003152
• 发表时间: 2013
• 期刊: PLoS genetics
• 影响因子: 4.5
• 作者: Chintakayala K;Singh SS;Rossiter AE;Shahapure R;Dame RT;Grainger DC
• 通讯作者: Grainger DC

Dimerization and DNA-dependent aggregation of the Escherichia coli nucleoid protein and chaperone CbpA.

• DOI: 10.1111/j.1365-2958.2010.07292.x
• 发表时间: 2010-09
• 期刊: Molecular microbiology
• 影响因子: 3.6
• 作者: Cosgriff S;Chintakayala K;Chim YT;Chen X;Allen S;Lovering AL;Grainger DC
• 通讯作者: Grainger DC

Chromosomal macrodomains and associated proteins: implications for DNA organization and replication in gram negative bacteria.

• DOI: 10.1371/journal.pgen.1002123
• 发表时间: 2011-06
• 期刊: PLoS genetics
• 影响因子: 4.5
• 作者: Dame RT;Kalmykowa OJ;Grainger DC
• 通讯作者: Grainger DC

DNA recognition by Escherichia coli CbpA protein requires a conserved arginine-minor-groove interaction.

• DOI: 10.1093/nar/gkv012
• 发表时间: 2015-02-27
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Chintakayala K;Sellars LE;Singh SS;Shahapure R;Westerlaken I;Meyer AS;Dame RT;Grainger DC
• 通讯作者: Grainger DC