COULD TRANSCRIPTION INDUCED MUTATIONS CAUSE CANCER?

描述：（改编自研究者摘要）可能存在 营养不良、转录、突变和癌症之间的联系。在 在哺乳动物中，许多基因响应于热量限制而被去抑制， 氨基酸限制也可以诱导基因表达， 突变率在一个模型系统中，转录的作用（由 四磷酸鸟苷或ppGpp）对突变率和亮氨酸突变的影响。 操纵子E.大肠杆菌进行检测。具体目标是确定：A. 对数生长期和亮氨酸代谢期mRNA周转的动力学 饥饿B。ppGpp对转录起始动力学的影响 leuB和pyrD. C.反义RNA和DNA对leuB的影响 拟议的调查有影响的理解机制， 突变和癌症据估计，大多数癌症是由 环境（包括营养）条件。数据表明 转录可以增加点突变和移码的速率， 这表明遗传去抑制可能是背景的主要原因， 突变。如果是这样的话，这种机制提供了代谢的关键环节， 营养不良引起的活动，并可以发挥指导作用， 突变发生了。关于单链DNA易受攻击性的基础研究 突变和修复可能很好地揭示了 肿瘤发生，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.