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1.
Adenosine diphosphate(ADP)-ribosylation is a unique post-translational modification that regulates many biological processes,such as DNA damage repair.During DNA repair,ADP-ribosylation needs to be reversed by ADP-ribosylhydrolases.A group of ADP-ribosylhydrolases have a catalytic domain,namely the macrodomain,which is conserved in evolution from prokaryotes to humans.Not all macrodomains remove ADP-ribosylation.One set of macrodomains loses enzymatic activity and only binds to ADP-ribose(ADPR).Here,we summarize the biological functions of these macrodomains in DNA damage repair and compare the structure of enzymatically active and inactive macrodomains.Moreover,small molecular inhibitors have been developed that target macrodomains to suppress DNA damage repair and tumor growth.Macrodomain proteins are also expressed in pathogens,such as severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).However,these domains may not be directly involved in DNA damage repair in the hosts or pathogens.Instead,they play key roles in pathogen replication.Thus,by targeting macrodomains it may be possible to treat pathogen-induced diseases,such as coronavirus disease 2019(COVID-19). 相似文献
2.
SIRT1（sirtuin 1）通过对肿瘤抑制蛋白和DNA损伤修复蛋白去乙酰化而使之失活。因此,SIRT1早期被认为是肿瘤促进因子。近来研究又表明SIRT1在某些肿瘤中表达降低且SIRT1缺乏导致遗传不稳定和肿瘤发生。超表达SIRT1可降低癌变风险。SIRT1的这种双重作用可能与其组织中SIRT1上游和下游因子的时空分布不同有关。 相似文献
3.
Genome stability can be threatened by both endogenous and exogenous agents.Organisms have evolved numerous mechanisms to repair DNA damage,including homologous recombination(HR)and non-homologous end joining(NHEJ).Among the factors associated with DNA repair,the MRE11-RAD50-NBS1(MRN)complex(MRE11-RAD50-XRS2 in Saccharomyces cerevisiae)plays important roles not only in DNA damage recognition and signaling but also in subsequent HR or NHEJ repair.Upon detecting DNA damage,the MRN complex activates signaling molecules,such as the protein kinase ataxia-telangiectasia mutated(ATM),to trigger a broad DNA damage response,including cell cycle arrest.The nuclease activity of the MRN complex is responsible for DNA end resection,which guides DNA repair to HR in the presence of sister chromatids.The MRN complex is also involved in NHEJ,and has a species-specific role in hairpin repair.This review focuses on the structure of the MRN complex and its function in DNA damage repair. 相似文献
4.
DNA-damage response network at the crossroads of cell-cycle checkpoints,cellular senescence and apoptosis 总被引：2，自引：0，他引：2
Schmitt E Paquet C Beauchemin M Bertrand R 《Journal of Zhejiang University. Science. B》2007,8(6):377-397
Tissue homeostasis requires a carefully-orchestrated balance between cell proliferation, cellular senescence and cell death. Cells proliferate through a cell cycle that is tightly regulated by cyclin-dependent kinase activities. Cellular senescence is a safeguard program limiting the proliferative competence of cells in living organisms. Apoptosis eliminates unwanted cells by the coordinated activity of gene products that regulate and effect cell death. The intimate link between the cell cycle, cellular senescence, apoptosis regulation, cancer development and tumor responses to cancer treatment has become eminently apparent. Extensive research on tumor suppressor genes, oncogenes, the cell cycle and apoptosis regulatory genes has revealed how the DNA damage-sensing and -signaling pathways, referred to as the DNA-damage response network, are tied to cell proliferation, cell-cycle arrest, cellular senescence and apoptosis. DNA-damage responses are complex, involving ＂sensor＂ proteins that sense the damage, and transmit signals to ＂transducer＂ proteins, which, in turn, convey the signals to numerous ＂effector＂ proteins implicated in specific cellular pathways, including DNA repair mechanisms, cell-cycle checkpoints, cellular senescence and apoptosis. The Bcl-2 family of proteins stands among ＂the mos＂t crucial regula＂tors of apop＂tosis and performs vi＂tal func＂tions in deciding whether a cell will live or die after cancer chemotherapy and irradiation. In addition, several studies have now revealed that members of the Bcl-2 family also interface with the cell cycle, DNA repair/recombination and cellular senescence, effects that are generally distinct from their function in apoptosis. In this review, we report progress in understanding the molecular networks that regulate cell-cycle checkpoints, cellular senescence and apoptosis after DNA damage, and discuss the influence of some Bcl-2 family members on cell-cycle checkpoint regulation. 相似文献
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6.
马云彤 《西安文理学院学报》2010,13(1):44-47
拓扑异构酶Ⅰ在DNA翻译和转录过程中催化单链DNA的断裂和连接,从而松弛DNA超螺旋,促进复制与转录的进行．拓扑异构酶Ⅰ抑制剂能够阻断DNA链的再连接,结果导致TopⅠ断裂复合物的积累,抑制复制和转录,造成DNA损伤,从而激活DNA损伤检验点,抑制细胞生长和诱发凋亡。喜树碱是最早发现、也是最重要和最广泛使用的拓扑异构酶Ⅰ抑制剂．细胞周期中DNA损伤、修复和检验点应答的分子机制是目前生命科学研究热点,而喜树碱已成为进行相关研究的重要的药理学工具． 相似文献
7.
DNA is the hereditary material in humans and almost all other organisms. It is essential for maintaining accurate transmission of genetic information. In the life cycle, DNA replication, cell division, or genome damage, including that caused by endogenous and exogenous agents, may cause DNA aberrations. Of all forms of DNA damage, DNA double-strand breaks(DSBs) are the most serious. If the repair function is defective, DNA damage may cause gene mutation, genome instability, and cell chromosome loss, which in turn can even lead to tumorigenesis. DNA damage can be repaired through multiple mechanisms. Homologous recombination(HR) and non-homologous end joining(NHEJ) are the two main repair mechanisms for DNA DSBs. Increasing amounts of evidence reveal that protein modifications play an essential role in DNA damage repair.Protein deubiquitination is a vital post-translational modification which removes ubiquitin molecules or polyubiquitinated chains from substrates in order to reverse the ubiquitination reaction. This review discusses the role of deubiquitinating enzymes(DUBs) in repairing DNA DSBs. Exploring the molecular mechanisms of DUB regulation in DSB repair will provide new insights to combat human diseases and develop novel therapeutic approaches. 相似文献
8.
Hodgson S 《Journal of Zhejiang University. Science. B》2008,9(1):1-4
A small proportion of many cancers are due to inherited mutations in genes, which result in a high risk to the individual of developing specific cancers. There are several classes of genes that may be involved: tumour suppressor genes, oncogenes, genes encoding proteins involved in DNA repair and cell cycle control, and genes involved in stimulating the angiogenic pathway. Alterations in susceptibility to cancer may also be due to variations in genes involved in carcinogen metabolism. This review discusses examples of some of these genes and the associated clinical conditions caused by the inheritance of mutations in such genes. 相似文献
9.
USP11通过去泛素化p53调控p53稳定性 总被引：2，自引：0，他引：2
Jia-ying KE ;Cong-jie DAI ;Wen-lin WU ;Jin-hua GAO ;Ai-juan XIA ;Guang-ping LIU ;Kao-sheng LV ;Chun-lin WU 《Journal of Zhejiang University. Science. B》2014,15(12):1032-1038
研究目的：深入研究p53的泛素化及稳定性的调控。创新要点：发现一个新的调控p53去泛素化的酶USPll,它可以通过与p53的结合去泛素化并稳定p53,从而揭示了一个新的p53去泛素化调控的机制。研究方法：通过免疫共沉淀发现p53可以与USP11结合（图1a）,通过泛素化检测试验发现USPI1可以去泛素化p53（图3a和3b）,最后通过逆转录．聚合酶链式反应（RT—PCR）试验发现在DNA损伤后,USP11对p53转录活性的提高是非常重要的。 相似文献
10.
Alkylated DNA lesions, induced by both exogenous chemical agents and endogenous metabolites, represent a major form of DNA damage in cells. The repair of alkylation damage is critical in all cells because such damage is cytotoxic and potentially mutagenic. Alkylation chemotherapy is a major therapeutic modality for many tumors, underscoring the importance of the repair pathways in cancer cells. Several different pathways exist for alkylation repair, including base excision and nucleotide excision repair, direct reversal by methyl-guanine methyltransferase(MGMT), and dealkylation by the AlkB homolog(ALKBH) protein family. However, maintaining a proper balance between these pathways is crucial for the favorable response of an organism to alkylating agents. Here, we summarize the progress in the field of DNA alkylation lesion repair and describe the implications for cancer chemotherapy. 相似文献
11.
Proteomic analysis of human umbilical vein endothelial cells exposed to PM<Subscript>2.5</Subscript>
Ji Zhu Lin-wen-si Zhu Jin-huan Yang Ying-ling Xu Cui Wang Zhuo-yu Li Wei Mao De-zhao Lu 《Journal of Zhejiang University. Science. B》2018,19(6):458-470
Exposure to fine ambient particulate matter (PM2.5) is known to be associated with cardiovascular disease. To uncover the molecular mechanisms involved in cardiovascular toxicity of PM2.5, we investigated alterations in the protein profile of human umbilical vein endothelial cells (HUVECs) treated with PM2.5 using two-dimensional electrophoresis in conjunction with mass spectrometry (MS). A total of 31 protein spots were selected as differentially expressed proteins and identified by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) MS. The results demonstrated that DNA damage and cell apoptosis are important factors contributing to PM2.5-mediated toxicity in HUVECs. It is further proposed that PM2.5 can inhibit superoxide dismutase (SOD) activity and increase reactive oxygen species (ROS) and malonaldehyde (MDA) production in a concentration-dependent manner. Induction of apoptosis and DNA damage through oxidative stress pathways may be one of the key toxicological events occurring in HUVECs under PM2.5 stress. These results indicated that the toxic mechanisms of PM2.5 on cardiovascular disease are related to endothelial dysfunction. 相似文献
12.
文章对西南交通大学下属的6个独立学院自2003年至2007年期间开设的精品课程中教师进行统计,研究了5年内6个学院所开设的精品课程中教师合作所形成的网络。基于轴辐式网络模型形成的6个教师合作网络一个是连通网络,而多数网络则是由多个子网络构成的非连通网络,各网络统计参数呈现出无标度网络特性,部分连通子网络呈现小世界网络特性,比较分析了造成各个网络特性差异的网络连接结构及其内在原因。 相似文献
13.
众所周知 ,DNA是遗传信息的携带者 ,遗传现象主要是由基因决定的。但是 ,近几年来科学家发现 ,朊病毒是一种可遗传的蛋白质粒子 ;DNA甲基化也导致一些遗传现象的发生 ;性状间的相互制约也可引起不受基因控制的表型出现……这些现象说明DNA并非遗传的全部。 相似文献
14.
近年认知神经心理学家利用神经成像技术对联觉进行了大脑激活情况研究,通过以颜色联觉为主的研究成果的对比与分析,发现联觉伴随体验的大脑激活不局限于特定区域(比如V4或顶叶区域),而是涉及一个大脑区域网络(大脑的6个区域被激活),这个大脑区域网络与联觉的三个不同加工过程相关联。同时通过对造成大脑结构差异的遗传基因研究进行总结与分析,发现找到的几个备选基因都是大脑中影响连接发展的基因,据此推测决定联觉的基因可能在大脑中影响连接发展的那些基因中(至少部分)找到。 相似文献
15.
近年来,研究冷和超冷原子碰撞已经由相同原子扩展到了异核原子领域.针对133Cs和Rb原子的碰撞,构建了两种异核原子间相互作用势,这两种势有相同的相移.另外,对39K原子间相互作用势进行实验和理论上的研究,构建了目前为止最精确的相互作用势能曲线.基于构建的势能曲线,并对133Cs和85Rb原子以及两39K原子间的冷和超冷碰撞特性进行了详细的研究,得到了非常满意的结果. 相似文献
16.
The 2015 Nobel Prize in Chemistry was awarded jointly to Tomas Lindahl, Paul Modrich and Aziz Sancar to honour their accomplishments in the field of DNA repair. Ever since the discovery of DNA structure and their importance in the storage of genetic information, questions about their stability became pertinent. A molecule which is crucial for the development and propagation of an organism must be closely monitored so that the genetic information is not corrupted. Thanks to the pioneering research work of Lindahl, Sancar, Modrich and their colleagues, we now have an holistic awareness of how DNA damage occurs and how the damage is rectified in bacteria as well as in higher organisms including human beings. A comprehensive understanding of DNA repair has proven crucial in the fight against cancer and other debilitating diseases. 相似文献
17.
在pH=7.40的Tris-HCl缓冲溶液中,采用荧光光谱法和粘度法研究了8-羟基喹啉（HQ）与鲱鱼精DNA的作用方式.用摩尔比法确定了HQ与DNA的结合比为12∶1.通过热力学研究得出,在27℃时HQ与DNA之间相互作用的Kφ27℃=3.844×105L/mol,热力学函数ΔrHφm=-5.08×104J/mol,ΔrGφm 300.15K=-3.2×104J/mol,ΔrSφm=-62.6 J/（mol.K）.结果显示该反应为焓驱动.实验表明HQ与DNA的作用方式为部分嵌插与静电作用方式. 相似文献
18.
自从Field和Song1989年初步建立了酵母双杂交系统以来，双杂交技术特别是酵母双杂交技术得到了长足的发展，衍生出了单杂交系统，三杂交系统，双诱饵系统等一系列相关的技术，使其真正成为分子生物学研究中广泛应用的技术手段，这些技术的应用有力地推动了蛋白质与蛋白质，蛋白质与小分子多肽，蛋白质与DNA分子间相互作用的研究，特别是在后基因组时代，对生命活动中蛋白质相互作用的网络信息研究，双杂交系统将发展更重要的作用。 相似文献
19.
Maintenance of cellular homeostasis and genome integrity is a critical responsibility of DNA double-strand break(DSB)signaling.P53-binding protein 1(53BP1)plays a critical role in coordinating the DSB repair pathway choice and promotes the non-homologous end-joining(NHEJ)-mediated DSB repair pathway that rejoins DSB ends.New insights have been gained into a basic molecular mechanism that is involved in 53BP1 recruitment to the DNA lesion and how 53BP1 then recruits the DNA break-responsive effectors that promote NHEJ-mediated DSB repair while inhibiting homologous recombination(HR)signaling.This review focuses on the up-and downstream pathways of 53BP1 and how 53BP1 promotes NHEJ-mediated DSB repair,which in turn promotes the sensitivity of poly(ADP-ribose)polymerase inhibitor(PARPi)in BRCA1-deficient cancers and consequently provides an avenue for improving cancer therapy strategies. 相似文献
20.
杨淋 《蒙自师范高等专科学校学报》1991,(2)
EDSS在0—10GHz频率范围内观察到水解DNA的微波共振吸收,这一尚有争议的结果引起许多学者浓厚的兴趣,并在理论和实验方面做了大量的工作。本文从理论上详细地研究了水解DNA的微波共振吸收问题。然后考虑DNA和抗衡离子的长程库仑作用及界面影响,计入水合层的阻尼作用及有关的耦合,自然地计算了DNA、水合层以及它们之间的静电相互作用,提出了一个更符合实际的模型,得到DNA和第一水合层系统的二阶非线性微分方程。在实际出现的小振幅振动下,方程中的非线性项为小项,用摄动法求解微分方程,计算出各级近似下解的具体形式。当外加电磁场在系统上后,得到了一系列的共振频率,许多与Van Zandt等人用局部有效场近似方法的结果一致,同时尚预言了一些新的共振频率。我们的模型与EDSS所讨论的对象相同,但计算结果没有他们所观察到的共振频率,故我们的工作似乎不支持Edwards等人的工作。 相似文献