作者机构:
[Wang, Wuzhou; He, Shuya; Shen, Wangtao; Qi, Huizhou; Ma, Yun] Univ South China, Inst Biochem & Mol Biol, Hengyang Med Coll, Hengyang 421001, Peoples R China.;[Qi, Huizhou] Univ South China, Hengyang Med Coll, Funct Lab Ctr, Hengyang 421001, Peoples R China.;[Wang, Wuzhou; He, Shuya; Qi, Huizhou; Xiao, Fangzhu] Univ South China, Hengyang Key Lab Biol Effects Nucl Radiat, Hengyang 421001, Peoples R China.;[Zhu, Hui] Univ South China, Inst Engn Math, Math & Phys Coll, Hengyang 421001, Peoples R China.;[He, Junyan] Univ South China, Affiliated Hosp 1, Dept Radiat Oncol, Hengyang 421001, Peoples R China.
通讯机构:
[Ma, Yun] I;[He, Shuya] H;Institute of Biochemistry and Molecular Biology, Hengyang Medical College, University of South China, Hengyang, 421001, China. Electronic address:;Hengyang Key Laboratory for Biological Effects of Nuclear Radiation, University of South China, Hengyang, 421001, China. Electronic address:
关键词:
DNA double-strand break;Mathematical model;DSB reaction intermediate;Kinetics of DSB repair
摘要:
This manuscript outlines the kinetics of two main repair pathways of DNA double-strand break (DSB) in eukaryotes: non-homologous end joining (NHEJ) and homologous recombination repair (HRR). In this review, we discuss the precise study of recruitment kinetics of repair proteins based on the latest technologies in the past two decades. Then we simulate the theoretical description of the DNA repair process by mathematical models. In our study, the consecutive reactions chain (CRC) model and continuous-time random walk (CTRW) model have been unified by us, so that we can obtain the function of the number of intermediates with time in the same framework of equations, overcome the incompatibility between the two models. On this basis, we propose a data fitting workflow using these both models. Finally, we give an overview of different real-time quantitative methods and the new mechanism complexity that can be found from the corresponding dynamic models.
期刊:
Research in Microbiology,2020年171(2):45-54 ISSN:0923-2508
通讯作者:
He, Shu-ya
作者机构:
[He, Shu-ya; Wang, Wu-zhou; He, Jun-yan; Ma, Yun; Qi, Hui-zhou] Univ South China, Hengyang Med Coll, Inst Biochem & Mol Biol, Hengyang 421001, Peoples R China.;[Qi, Hui-zhou] Univ South China, Hengyang Med Coll, Funct Lab Ctr, Hengyang 421001, Peoples R China.;[He, Shu-ya; Wang, Wu-zhou; He, Jun-yan; Xiao, Fang-zhu; Qi, Hui-zhou] Univ South China, Hengyang Key Lab Biol Effects Nucl Radiat, Hengyang 421001, Peoples R China.
通讯机构:
[He, Shu-ya] U;Univ South China, Hengyang Key Lab Biol Effects Nucl Radiat, Hengyang 421001, Peoples R China.
关键词:
Antioxidative system;Deinococcus radiodurans;Manganese;PprI;PprM;Reactive oxygen species
摘要:
Deinococcus radiodurans is famous for its extreme resistance to various stresses such as ionizing radiation (IR), desiccation and oxidative stress. The underlying mechanism of exceptional resistance of this robust bacterium still remained unclear. However, the antioxidative system of D. radiodurans has been considered to be the determinant factor for its unparalleled resistance and protects the proteome during stress, then the DNA repair system and metabolic system exert their functions to restore the cell to normal physiological state. The antioxidative system not only equipped with the common reactive oxygen species (ROS) scavenging enzymes (e.g. catalase and superoxide dismutase) but also armed with a variety of non-enzyme antioxidants (e.g. carotenoids and manganese species). And the small manganese complexes play an important role in the antioxidative system of D. radiodurans. Recent studies have characterized several regulators (e.g., PprI and PprM) in D. radiodurans, which play critical roles in the protection of the bacteria from various stresses. In this review, we offer a panorama of the progress regarding the characteristics of the antioxidative system in D. radiodurans and its application in the future.
期刊:
Medical Hypotheses,2018年119:37-40 ISSN:0306-9877
通讯作者:
He, Shu-ya
作者机构:
[He, Shu-ya; Wang, Wu-zhou; He, Jun-yan; Ma, Yun; Qi, Hui-zhou] Univ South China, Med Coll, Hengyang, Peoples R China.;[He, Shu-ya; Wang, Wu-zhou; He, Jun-yan; Ma, Yun] Univ South China, Dept Biochem & Mol Biol, Hengyang 421001, Peoples R China.
通讯机构:
[He, Shu-ya] U;Univ South China, Dept Biochem & Mol Biol, Hengyang 421001, Peoples R China.
摘要:
Radiation-induced enteritis is one of the most common complications in patients under radiotherapy at abdominal or pelvic cavity. Up to 50% of patients treated with pelvic radiotherapy has been reported radiation-induced acute enteritis, and half of them developed chronic enteritis. Overproduction of free radicals, activation of inflammatory pathways and vascular endothelial dysfunction were considered as the primary mechanisms of radiation-induced enteritis. Because probiotics have been demonstrated as a promising potential candidate for treating intestinal diseases, it may be a safer and more effective radioprotector for the enteritis compared to conventional chemical agents with inherent toxicities. Here, we propose that a recombinant Lactobacillus sakei would decrease the complications or symptoms significantly through against different pathogenic mechanisms simultaneously. Therefore, application of higher radiation dose for tumor control would be feasible when co-treating with recombinant Lactobacillus sakei.
摘要:
Deinococcus radiodurans has attracted a great interest in the past decades due to its extraordinary resistance to ionizing radiation and highly efficient DNA repair system. Recent studies indicated that pprM is a putative pleiotropic gene in D. radiodurans and plays an important role in radioresistance and antioxidation, but its underlying mechanisms are poorly elucidated. In this study, pprM mutation was generated to investigate resistance to desiccation and oxidative stress. The result showed that the survival of pprM mutant under desiccation was markedly retarded compared to the wild strain from day 7–28. Furthermore, knockout of pprM increases the intercellular accumulation of ROS and the sensibility to H2O2 stress in the bacterial growth inhibition assay. The absorbance spectrum experiment for detecting the carotenoid showed that deinoxanthin, a carotenoid that peculiarly exists in Deinococcus, was reduced in the pprM mutant in the pprM mutant. Quantitative real time PCR showed decreased expression of three genes viz. CrtI (DR0861, 50%),CrtB (DR0862, 40%) and CrtO (DR0093, 50%), which are involved in deinoxanthin synthesis, and of Dps (DNA protection during starving) gene (DRB0092) relevant to ion combining and DNA protection in cells. Our results suggest that pprM may affect antioxidative ability of D. radiodurans by regulating the synthesis of deinoxanthin and the concentration of metal ions. This may provide new clues for the treatment of antioxidants.
作者机构:
[He, Shuya; Xiao, Xiao; Fu, Liang; Ma, Yun; Tian, Shuai] Univ South China, Dept Biochem & Biol, 28 Western Changsheng Rd, Hengyang City 421001, Hunan, Peoples R China.;[Wang, Zongbao; He, Shuya; Lei, Xiaoyong; Ma, Yun; Lei, XY] Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, 28 Western Changsheng Rd, Hengyang City 421001, Hunan, Peoples R China.;[Chen, Qiong] Cent S Univ, Xiangya Hosp, Dept Resp, Dept Geriatr Med, Changsha 410008, Hunan, Peoples R China.
通讯机构:
[He, Shuya] U;[Ma, Y; Lei, XY] H;Univ South China, Dept Biochem & Biol, 28 Western Changsheng Rd, Hengyang City 421001, Hunan, Peoples R China.;Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, 28 Western Changsheng Rd, Hengyang City 421001, Hunan, Peoples R China.
关键词:
miR-19b;FXR1;RAB18;USP32;Dusp6
摘要:
The biological effects of microRNAs (miRNAs) in the Fragile X Syndrome (FXS) have been widely studied. Dysregulation of miRNAs plays a critical role in the progression of nervous system diseases and in cell proliferation and differentiation. Our previous study validated that miR-19b-3p was associated with FXR1 (Fragile X related gene I), one of homologous genes of FMR1 (Fragile X mental retardation 1). The purpose of this study was to investigate the relationship of FXR1 and miR-19b-3p, and the crucial role of miR-19b-3p in FXS and to validate whether miR-19b-3p could regulate the growth of SH-SY5Y cells. We determined that miR-19b-3p could regulate the expression of not only USP32, RAB18 and Dttsp6 but also FXR1, and FXR1 could in turn regulate the expression of miR-19b-3p. What's more, the overexpression of miR-19b-3p significantly inhibited the proliferation, contributed the apoptosis and slowed down the cycle of SH-SY5Y cells. Taken together, our results indicate that miR-19b-3p plays a significant role in the molecular pathology of FXS by interacting with FXR1 and influencing the growth of SH-SY5Y cells. (C) 2016 Elsevier B.V. All rights reserved.
通讯机构:
[Ma, Y; He, SY] U;Univ South China, Dept Biochem & Biol, 28 Western Changshen Rd, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Inst Pharmaceut & Biol Sci, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Hunan, Peoples R China.
关键词:
fragile X related protein 1;CMP-N-acetylneuraminic acid synthetase;fragile X syndrome;GM1
摘要:
Fragile X mental retardation protein (FMRP), fragile X related 1 protein (FXR1P) and FXR2P are the members of the FMR protein family. These proteins contain two KH domains and a RGG box, which are characteristic of RNA binding proteins. The absence of FMRP, causes fragile X syndrome (FXS), the leading cause of hereditary mental retardation. FXR1P is expressed throughout the body and important for normal muscle development, and its absence causes cardiac abnormality. To investigate the functions of FXR1P, a screen was performed to identify FXR1P-interacting proteins and determine the biological effect of the interaction. The current study identified CMP-N-acetylneuraminic acid synthetase (CMAS) as an interacting protein using the yeast two-hybrid system, and the interaction between FXR1P and CMAS was validated in yeast using a beta-galactosidase assay and growth studies with selective media. Furthermore, co-immunoprecipitation was used to analyze the FXR1P/CMAS association and immunofluorescence microscopy was performed to detect expression and intracellular localization of the proteins. The results of the current study indicated that FXR1P and CMAS interact, and colocalize in the cytoplasm and the nucleus of HEK293T and HeLa cells. Accordingly, a fragile X related 1 (FXR1) gene overexpression vector was constructed to investigate the effect of FXR1 overexpression on the level of monosialotetrahexosyl-ganglioside 1 (GM1). The results of the current study suggested that FXR1P is a tissue-specific regulator of GM1 levels in SH-SY5Y cells, but not in HEK293T cells. Taken together, the results initially indicate that FXR1P interacts with CMAS, and that FXR1P may enhance the activation of sialic acid via interaction with CMAS, and increase GM1 levels to affect the development of the nervous system, thus providing evidence for further research into the pathogenesis of FXS.
作者机构:
[Tian Shuai; Ma Yun] Univ South China, Dept Biochem & Biol, Hengyang 421001, Peoples R China.;[Ma Yun] Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.
通讯机构:
[Ma Yun] U;[Ma Yun] H;Univ South China, Dept Biochem & Biol, Hengyang 421001, Peoples R China.;Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.
关键词:
脆性X综合征;FXR1P学科
摘要:
脆性X综合征(fragile X syndrome,FXS)是最常见的遗传性认知障碍疾病,也是一种与自闭症谱系障碍(autism spectrum disorder,ASD)相关的严重的基因疾病.它主要是由于脆性X智力低下基因1(fragile X mental retardation 1,FMR1)的异常扩增及其上游CpG岛的异常甲基化,导致其编码的脆性X智力低下蛋白(fragile X mental retardation protein,FMRP)表达减少或缺失引起的.FMRP与miRNA(microRNA)均具有翻译抑制活性,而且FMRP在生物化学和遗传学上均与miRNA调控通路有相互作用.此外,越来越多的研究发现miRNA调控通路在FXS的发病和治疗中发挥作用.因此,本文对miRNA的功能及其与脆性X蛋白家族成员间的相互作用进行阐述,为在miRNA水平了解FXS的发病机制奠定基础.