Regulation of DNA replication in B.subtilis by YabA

YabA 对枯草芽孢杆菌 DNA 复制的调节

• 批准号: 7908241
• 负责人: Houra Merrikh
• 金额: $ 4.76万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7908241
• 关键词: Bacteria; Chromosomes; Cowpox; DNA biosynthesis; Frequencies; Goals; Gram-Positive Bacteria; Growth; In Vitro; Location; Pathogenesis; Process; Regulation; Replication Initiation; Replication Origin; Series; Subgroup; Time; helicase; human disease; in vivo; insight; pathogenic bacteria; public health relevance; research study

DESCRIPTION (provided by applicant): The mechanism(s) used to control the timing and frequency of replication initiation in Gram positive bacteria are unknown. YabA is a negative regulator of replication initiation in B. subtilis, and is conserved in other Gram positive bacteria. The mechanism by which YabA carries out its regulatory function is not yet understood. I found that YabA associates with the chromosomal origin of replication (oriC), and is delivered there at a step following the loading of the replicative helicase. I propose a series of experiments to identify the factor(s) necessary for association of YabA with oriC. I also propose experiments to determine if the subcellular location of YabA and its association with the chromosome changes during the replication cycle. These experiments should provide insights into the timing of YabA's function in inhibition of replication initiation. Finally, I propose several in vivo and in vitro experiments to determine the mechanism of inhibition of replication initiation by YabA. PUBLIC HEALTH RELEVANCE: Regulation of DNA replication is critical for survival and growth, and is generally achieved by controlling the timing and frequency of replication initiation. The mechanisms behind this kind of control remain elusive in a large subset of bacteria known as Gram-positives, a subgroup of which contribute to pathogenesis and human disease. The goal of this project is to study one of the mechanisms behind DNA replication control, and the results of this proposal could contribute to better understanding of these processes, as well as provide general insights into replication control in pathogenic bacteria.

描述(申请人提供)：用于控制革兰氏阳性细菌复制启动的时间和频率的机制(S)尚不清楚。Yaba是枯草杆菌复制起始的负调控因子，在其他革兰氏阳性菌中也是保守的。Yaba执行其调控功能的机制尚不清楚。我发现Yaba与染色体复制起点(ORIC)有关，并在复制解旋酶加载后的一个步骤中递送到那里。我建议进行一系列实验，以确定将八巴与奥利克联系起来所必需的因素(S)。我还建议进行实验，以确定Yaba的亚细胞位置及其与染色体的关系是否在复制周期中发生变化。这些实验应该为Yaba在抑制复制启动中作用的时机提供洞察力。最后，我提出了几个体内和体外实验，以确定Yaba抑制复制启动的机制。 公共卫生相关性：对DNA复制的调控对生存和生长至关重要，通常通过控制复制启动的时间和频率来实现。在一大类被称为革兰氏阳性菌的细菌中，这种控制背后的机制仍然难以捉摸，革兰氏阳性菌是导致发病和人类疾病的一个亚群。这个项目的目标是研究DNA复制控制背后的机制之一，这一建议的结果可能有助于更好地了解这些过程，并为病原菌的复制控制提供一般的见解。