Eukaryotic cells contain numerous iron-requiring pro- teins such as iron-sulfur （Fe-S） cluster proteins, hemoproteins and ribonucleotide reductases （RNRs）. These proteins utilize iron as a cofactor and perform key...Eukaryotic cells contain numerous iron-requiring pro- teins such as iron-sulfur （Fe-S） cluster proteins, hemoproteins and ribonucleotide reductases （RNRs）. These proteins utilize iron as a cofactor and perform key roles in DNA replication, DNA repair, metabolic catalysis, iron regulation and cell cycle progression. Disruption of iron homeostasis always impairs the functions of these iron- requiring proteins and is genetically associated with diseases characterized by DNA repair defects in mam- mals. Organisms have evolved multi-layered mecha- nisms to regulate iron balance to ensure genome stability and cell development. This review briefly pro- vides current perspectives on iron homeostasis in yeast and mammals, and mainly summarizes the most recent understandings on iron-requiring protein functions involved in DNA stability maintenance and cell cycle control.展开更多
Excess iron is tightly associated with tumorigenesis in multiple human cancer types through a variety of mechanisms including catalyzing the formation of mutagenic hydroxyl radicals, regulating DNA replica- tion, repa...Excess iron is tightly associated with tumorigenesis in multiple human cancer types through a variety of mechanisms including catalyzing the formation of mutagenic hydroxyl radicals, regulating DNA replica- tion, repair and cell cycle progression, affecting signal transduction in cancer cells, and acting as an essential nutrient for proliferating tumor cells, Thus, multiple therapeutic strategies based on iron deprivation have been developed in cancer therapy, During the past few years, our understanding of genetic association and molecular mechanisms between iron and tumorigenesis has expanded enormously. In this review, we briefly summarize iron homeostasis in mammals, and discuss recent progresses in understanding the aberrant iron metabolism in numerous cancer types, with a focus on studies revealing altered signal transduction in cancer cells.展开更多
文摘Eukaryotic cells contain numerous iron-requiring pro- teins such as iron-sulfur （Fe-S） cluster proteins, hemoproteins and ribonucleotide reductases （RNRs）. These proteins utilize iron as a cofactor and perform key roles in DNA replication, DNA repair, metabolic catalysis, iron regulation and cell cycle progression. Disruption of iron homeostasis always impairs the functions of these iron- requiring proteins and is genetically associated with diseases characterized by DNA repair defects in mam- mals. Organisms have evolved multi-layered mecha- nisms to regulate iron balance to ensure genome stability and cell development. This review briefly pro- vides current perspectives on iron homeostasis in yeast and mammals, and mainly summarizes the most recent understandings on iron-requiring protein functions involved in DNA stability maintenance and cell cycle control.
文摘Excess iron is tightly associated with tumorigenesis in multiple human cancer types through a variety of mechanisms including catalyzing the formation of mutagenic hydroxyl radicals, regulating DNA replica- tion, repair and cell cycle progression, affecting signal transduction in cancer cells, and acting as an essential nutrient for proliferating tumor cells, Thus, multiple therapeutic strategies based on iron deprivation have been developed in cancer therapy, During the past few years, our understanding of genetic association and molecular mechanisms between iron and tumorigenesis has expanded enormously. In this review, we briefly summarize iron homeostasis in mammals, and discuss recent progresses in understanding the aberrant iron metabolism in numerous cancer types, with a focus on studies revealing altered signal transduction in cancer cells.
文摘低剂量超辐射敏感(HRS)和诱导辐射抗性(IRR)是辐射生物学的两个重要现象,研究这两个现象发生的机理对于辐射保护、控制肿瘤发生、研制新的功能材料具有重要的意义。辐射产生的DNA双链断裂(DNA double-strand breaks,DSBs)是辐射诱导细胞失活的主要损伤形式。对DSBs不能进行修复或者不能进行正确的重新连接是引起细胞死亡的主要原因。与DNA合成前期(first gap phase,G1期)和DNA合成期(synthetic phase,S期)相比,HRS在DNA合成后期(second gap phase,G2期)的表现非常明显。HRS和IRR之间相互转换调控的机制可能是G2期细胞中的一部分存在一个激活过程的发生。DNA损伤修复机制在HRS/IRR过程中发挥了重要作用。在低于20cGy的剂量条件下,细胞产生效率较低的损伤效应,细胞死亡迅速增加,低剂量超辐射敏感现象(HRS)出现;在高于20cGy的条件下,辐射造成DNA双链断裂,这些DSB本身或者由辐射引起的DNA变化激活了ATM(ataxia telangiectasia mutated),G2期专有的检测点被激活,细胞周期在G2期停顿下来,激活的G2期专有的检测点促进对DNA进行修复,提高了细胞的存活率,此时,诱导辐射抗性(IRR)出现。尽管这些结果使人们对HRS/IRR有了一个比较清晰地了解,目前仍然存在着一些关键问题有待解决。例如,为什么有些细胞系表现HRS/IRR现象,而有些细胞系不表现HRS/IRR现象;细胞中是否存在针对单一剂量的突变的HRS/IRR等。这些问题可能是将来重要的研究方向。
