COULD TRANSCRIPTION INDUCED MUTATIONS CAUSE CANCER?

描述：(改编自调查人员的摘要)可能会有一个 营养不良、转录、突变和癌症之间的联系。在……里面 在哺乳动物中，许多基因在卡路里限制的反应下被解除抑制， 而氨基酸限制也可以诱导基因表达，从而增加 突变率。在模型系统中，转录的效果(由 鸟苷四磷酸(PpGpp)对亮氨酸突变率和突变的影响 将对大肠杆菌操纵子进行检查。具体目标是确定：A. 对数生长期和亮氨酸期信使核糖核酸周转动力学 饿死了。B.ppGpp对小鼠脑内转录启动动力学的影响 LeuB和PyrD。C.反义RNA和DNA对LeuB的影响。 拟议的调查对理解 突变和癌症。据估计，大多数癌症是由 受环境(包括营养)条件的影响。数据表明， 转录可以增加点突变和移码的频率， 这表明基因去抑制可能是背景的一个主要原因 突变。如果是这样，这种机制提供了新陈代谢的关键环节 由营养不良引起的活动，并可能在指导 突变就会发生。单链DNA易感性的基础研究 突变和修复可能很好地揭示了对 肿瘤的发生，从而有助于预防或治疗癌症。

DESCRIPTION: (Adapted from the investigator's abstract) There may be a connection between malnutrition, transcription, mutations and cancer. In mammals, a number of genes are derepressed in response to caloric restrictions, and amino acid limitation can also induce gene expression, which increases mutation rates. In a model system, the effect of transcription (activated by guanosine tetraphosphate, or ppGpp) on mutation rates and mutations in the leu operon of E. coli will be examined. Specific aims are to determine the: A. Kinetics of mRNA turnover during logarithmic growth and during leucine starvation. B. Effect of ppGpp on the kinetics of transcription initiation in leuB and pyrD. C. Effect of antisense RNA and DNA on leuB. The proposed investigations have implications for understanding mechanisms of mutations and cancer. It is estimated that the majority of cancers are caused by environmental (including nutritional) conditions. Data indicate that transcription can enchance the rate of both point mutations and frameshifts, suggesting that genetic derepression may be a major cause of background mutations. If so, this mechanism provides the critical link to metabolic activities evoked by malnutrition, and could play a role in directing which mutations occur. Basic research on the vulnerability of single-stranded DNA to mutation and repair may well reveal insights into the mechanisms of tumorgenesis, and thus aid in the prevention or treatment of cancer.