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DNA Double-Strand Breaks,Potential Targets for HBV Integration 被引量:2
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作者 胡晓文 林菊生 +4 位作者 谢琼慧 任精华 常莹 吴文杰 夏羽佳 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2010年第3期265-270,共6页
Hepatitis B virus(HBV)-induced hepatocellular carcinoma(HCC) is one of the most fre-quently occurring cancers.Hepadnaviral DNA integrations are considered to be essential agents which can promote the process of the he... Hepatitis B virus(HBV)-induced hepatocellular carcinoma(HCC) is one of the most fre-quently occurring cancers.Hepadnaviral DNA integrations are considered to be essential agents which can promote the process of the hepatocarcinogenesis.More and more researches were designed to find the relationship of the two.In this study,we investigated whether HBV DNA integration occurred at sites of DNA double-strand breaks(DSBs),one of the most detrimental DNA damage.An 18-bp I-SceI homing endonuclease recognition site was introduced into the DNA of HepG2 cell line by stable DNA transfection,then cells were incubated in patients’ serum with high HBV DNA copies and at the same time,DSBs were induced by transient expression of I-SceI after transfection of an I-SceI expression vector.By using nest PCR,the viral DNA was detected at the sites of the break.It appeared that integra-tion occurred between part of HBV x gene and the I-SceI induced breaks.The results suggested that DSBs,as the DNA damages,may serve as potential targets for hepadnaviral DNA insertion and the integrants would lead to widespread host genome changes necessarily.It provided a new site to investi-gate the integration. 展开更多
关键词 DNA double-strand breaks hepatitis B virus INTEGRATION non-homologous end joining
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Comparison of DNA double-strand breaks induced by ^(16)O^(8+) in deproteinized DNA and intact cells
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作者 Zhou Guang-Ming Wei Zeng-Quan +4 位作者 Li Wen-Jian Gao Qing-Xiang He Jing Li Qiang Wang Ju-Fang (Institute of Modern Physics, the Chinese Academy of Sciences, Lanzhou 720000Department of Biology, Lanzhou University, Lanzhou 730000) 《Nuclear Science and Techniques》 SCIE CAS CSCD 1998年第4期235-238,共4页
The yield of DNA double-strand breaks (DSBs) is sure to be influenced by theenvironment around DNA molecule. Inverse pulsed-field gel electrophoresis (PIGE) has beenapplied to compare the sensitivity of B16 cells and ... The yield of DNA double-strand breaks (DSBs) is sure to be influenced by theenvironment around DNA molecule. Inverse pulsed-field gel electrophoresis (PIGE) has beenapplied to compare the sensitivity of B16 cells and their DNA in DSBs induced by 75 MeV/u16O8+ beam. Results show that the percentages of DNA released from the plug(PR) in bothkinds of tile samples increase with the dose and approach a similar quasi-threshold of about81%. A simple new equation was presented to calculate the break level of DNA molecules.Within a certain dose, the relationship between the break level and the dose is linear. Theyield of DSBs in deproteinized DNA was 1.11 DSBs/100 Mbp/Gy, while that in intact cells was0.60DSBs/100Mbp/Gy. It is testified that deproteinized DNA is more sensitive to oxygen ionsirradiation than intact cells. 展开更多
关键词 DNA 双链断开 ^16O^8+感应
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Application of Artificially Induced Double-strand Breaks (DSB) and Triplex-forming Oligonucleotides (TFO) in the Improvement of Gene Targeting Efficiency
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作者 Hegang LI Wenke CHENG +5 位作者 Ke JIANG Xiaoli REN Yongping JIANG Lele HOU Xiaojing HAO Jinshan ZHAO 《Agricultural Biotechnology》 CAS 2013年第1期1-6,12,共7页
Gene targeting technology is an important means to investigate gene functions, but its efficiency of gene targeting is very low, especially for somatic cell targeting. Artificially induced double-strand breaks (DSB)... Gene targeting technology is an important means to investigate gene functions, but its efficiency of gene targeting is very low, especially for somatic cell targeting. Artificially induced double-strand breaks (DSB) and triplex forming oligonucleotide (TFO) are currently developed methods to improve the targeting efficiency. This paper summarized the basic principles, design ideas and application in gene targeting efficiency improvement of these two methods, analyzed and com- pared their characteristics, and finally proposed prospects for their future development. 展开更多
关键词 Gene targeting double-strand breaks Zinc finger nuclease Homing endonuclease Triplex-forming oligonucleotides
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Exposure to Long Magnetic Resonance Imaging Thermometry Does Not Cause Significant DNA Double-Strand Breaks on CF-1 Mice
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作者 Christopher Brian Abraham Sepideh Dadgar +2 位作者 Wely B. Floriano Michael Campbell Laura Curiel 《Journal of Modern Physics》 2022年第6期839-850,共12页
The purpose of the study was to investigate if the high gradient strength and slew rate used for long MRI-thermometry monitoring could cause DNA double-stranded breaks (DSBs). To this end, an enzyme-linked immunosorbe... The purpose of the study was to investigate if the high gradient strength and slew rate used for long MRI-thermometry monitoring could cause DNA double-stranded breaks (DSBs). To this end, an enzyme-linked immunosorbent assay (ELISA) was used to quantify &gamma;H2AX, a molecular marker for DSBs, in the blood of mice after a 6-hour exposure to magnetic resonance imaging (MRI). Fourteen CF-1 female mice were separated into 4 experimental groups: Untreated negative control, MRI-treated, MRI-Control, and exposed to ionizing radiation positive control. Untreated negative control was used as a baseline for ELISA to quantify &gamma;H2AX. MRI-treated consisted of a 6-hour continuous magnetic resonance imaging (MRI) echo planar imaging (EPI) sequence with a slew rate of 192 mT/m/s constituting a significantly longer imaging time than routine clinical imaging. MRI-control mice were maintained under the same conditions outside the MRI scanner for 6-hours. Mice in the irradiation group served as a positive control of DSBs and were exposed to either 2 Gy, 5 Gy or 10 Gy of ionizing radiation. DSBs in the blood lymphocytes from the treatment groups were analyzed using the &gamma;H2AX ELISA and compared. Total protein concentration in lysates was determined for each blood sample and averaged 1 ± 0.35 mg/mL. Irradiated positive controls were used to test radiation dose-dependency of the &gamma;H2AX ELISA assay where a linear dependency on radiation exposure was observed (r<sup>2</sup> = 0.93) between untreated and irradiated samples. Mean and standard error mean of &gamma;H2AX formation were calculated and compared between each treatment group. Repeated measures 1-way ANOVA showed statistically significant differences between the means of irradiated controls and both the MRI-control and MRI-treated groups. There was no statistically significant difference between the MRI-treated samples and the MRI-control groups. Our results show that long MRI exposure at a high slew rate did not cause increased levels of &gamma;H2AX when compared to control mice, suggesting that no increase in DSBs was caused by the long MR thermometry imaging session. The novelty of this work contradicts other studies that have suggested MRI may cause DSBs;this work suggests an alternative cause of DNA damage. 展开更多
关键词 γH2AX DNA Damage MRI Thermometry GADOLINIUM double-stranded breaks (dsbs) ELISA Ionizing Radiation
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The role of NBS1 in DNA double strand break repair, telomere stability, and cell cycle checkpoint control 被引量:14
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作者 Ying Zhang Junqing Zhou Chang UK Lim 《Cell Research》 SCIE CAS CSCD 2006年第1期45-54,共10页
The genomes of eukaryotic cells are under continuous assault by environmental agents and endogenous metabolic byproducts. Damage induced in DNA usually leads to a cascade of cellular events, the DNA damage response. F... The genomes of eukaryotic cells are under continuous assault by environmental agents and endogenous metabolic byproducts. Damage induced in DNA usually leads to a cascade of cellular events, the DNA damage response. Failure of the DNA damage response can lead to development of malignancy by reducing the efficiency and fidelity of DNA repair. The NBS1 protein is a component of the MRE11/RAD50/NBS 1 complex (MRN) that plays a critical role in the cellular response to DNA damage and the maintenance of chromosomal integrity. Mutations in the NBS1 gene are responsible for Nijmegen breakage syndrome (NBS), a hereditary disorder that imparts an increased predisposition to development of malignancy. The phenotypic characteristics of cells isolated from NBS patients point to a deficiency in the repair of DNA double strand breaks. Here, we review the current knowledge of the role of NBS1 in the DNA damage response. Emphasis is placed on the role of NBS1 in the DNA double strand repair, modulation of the DNA damage sensing and signaling, cell cycle checkpoint control and maintenance oftelomere stability. 展开更多
关键词 Nijmegen breakage syndrome NBS 1 DNA damage response DNA double strand break cell cycle checkpoint control telomere maintenance
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DETECTION OF STRAND BREAKS OF DNA IN HUMAN EARLY CHORIONIC VILLUS CELLS INDUCED BY DIAGNOSTIC ULTRASOUND USING ^(32)P-LABELED ALU HYBRIDIZATION
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作者 王彩凤 李旭 张蕴璟 《Journal of Pharmaceutical Analysis》 SCIE CAS 2006年第1期57-60,共4页
Objective To explore if strand breaks of DNA in human early chorionic villus cells in uterus were induced by diagnostic ultrasound and to evaluate the method used for detection of single-stranded breaks and double-str... Objective To explore if strand breaks of DNA in human early chorionic villus cells in uterus were induced by diagnostic ultrasound and to evaluate the method used for detection of single-stranded breaks and double-stranded breaks in human DNA. Methods 60 normal pregnant women aged 20-30, who underwent artificial abortion during 6-8 weeks of gestation, were randomly divided into 2 experimental groups: All 30 cases were exposed to diagnostic ultrasound in uterus for 10 minutes, and 24 hours later chorionic villi were extracted; the other 30 cases were taken as the control group. Single-stranded DNA and double-stranded DNA in villus cells in all cases were isolated by the alkaline unwinding combined with hydroxylapatite chromatography, and were quantitatively detected using 32 P-labeled Alu probe for dot-blotting hybridization. Results There was no significant difference in quantity and percentage in single-stranded DNA and double-stranded DNA between 2 groups (P>0.05). 32 P-Alu probe could only hybridize with human DNA, and could detect DNA isolated from as few as 2.5×10 3 chorionic villus cells and 0.45ng DNA in human leukocytes. Conclusion The results suggested that there were no DNA strand damages in human chorionic villus cells when the uterus was exposed to diagnostic ultrasound for 10 minutes. The method,^(32)P-Alu probe for dot-blotting hybridization, was even more specific, sensitive and accurate than conventional approaches. 展开更多
关键词 diagnostic ultrasound early pregnancy chorionic villus in uterus DNA single-stranded breaks(ssbs) double-stranded breaks(dsbs) ^(32)P-labeled Alu probe dot-blot hybridization
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Maternal gene Ooep may participate in homologous recombination-mediated DNA double-strand break repair in mouse oocytes
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作者 Da-Jian He Lin Wang +5 位作者 Zhi-Bi Zhang Kun Guo Jing-Zheng Li Xie-Chao He Qing-Hua Cui Ping Zheng 《Zoological Research》 SCIE CAS CSCD 2018年第6期387-395,共9页
DNA damage in oocytes can cause infertility and birth defects. DNA double-strand breaks (DSBs) are highly deleterious and can substantially impair genome integrity. Homologous recombination (HR)-mediated DNA DSB r... DNA damage in oocytes can cause infertility and birth defects. DNA double-strand breaks (DSBs) are highly deleterious and can substantially impair genome integrity. Homologous recombination (HR)-mediated DNA DSB repair plays dominant roles in safeguarding oocyte quantity and quality. However, little is known regarding the key players of the HR repair pathway in oocytes. Here, we identified oocyte-specific gene Ooep as a novel key component of the HR repair pathway in mouse oocytes. OOEP was required for efficient ataxia telangiectasia mutated (ATM) kinase activation and Rad51 recombinase (RAD51) focal accumulation at DNA DSBs. Ooep null oocytes were defective in DNA DSB repair and prone to apoptosis upon exogenous DNA damage insults. Moreover, Ooep null oocytes exhibited delayed meiotic maturation. Therefore, OOEP played roles in preserving oocyte quantity and quality by maintaining genome stability. Ooep expression decreased with the advance of maternal age, suggesting its involvement in maternal aging. 展开更多
关键词 Ooep Homologous recombination DNA double-strand break repair ATM RAD51
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DNA聚合酶θ:易错的多功能DNA末端修复分子 被引量:1
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作者 王瑶 陈国江 +3 位作者 冯健男 石艳春 王晶 郑源强 《生物化学与生物物理进展》 SCIE CAS CSCD 北大核心 2024年第3期493-503,共11页
DNA聚合酶θ(DNA polymerase theta,Polθ)是一种广泛存在于动植物中的DNA修复酶。它在选择性末端连接(alternative end-joining,Alt-EJ)途径中发挥着关键作用,常参与DNA双链断裂(DNA double-strand breaks,DSB)损伤修复。在正常生理状... DNA聚合酶θ(DNA polymerase theta,Polθ)是一种广泛存在于动植物中的DNA修复酶。它在选择性末端连接(alternative end-joining,Alt-EJ)途径中发挥着关键作用,常参与DNA双链断裂(DNA double-strand breaks,DSB)损伤修复。在正常生理状态下,Polθ主要调控基因组稳定性。然而,在恶性肿瘤发生时,Polθ表现出异常高表达水平,并参与调控肿瘤细胞的恶性转变过程。研究表明,抑制Polθ活性可导致同源重组(homologous recombination,HR)缺陷的肿瘤细胞发生合成致死(synthetic lethality,SL)。因此,已经开发出多种针对Polθ的小分子抑制剂,可与其他化疗药物联合使用以抑制恶性肿瘤的发展。此外,敲除或抑制Polθ活性还能增加HR修复效率,从而提高外源基因靶向整合效果。本文综述了Polθ及其介导的Alt-EJ修复机制在生物学功能方面的最新研究进展,为靶向Polθ在肿瘤治疗和基因编辑方面的应用提供理论基础。 展开更多
关键词 DNA聚合酶θ DNA双链断裂修复 基因组稳定性 肿瘤抑制 靶向整合
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精准序列替换基因组编辑技术研究进展 被引量:1
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作者 许永汉 齐泽宇 +2 位作者 李文静 赵啊慧 武德传 《云南农业大学学报(自然科学版)》 CAS CSCD 北大核心 2024年第2期162-175,共14页
利用基因组编辑技术可以对微生物、动植物和人类细胞系基因组进行精准的序列替换,加速生物育种进程和遗传性疾病治疗,从而在农业生产和医疗上取得突破。基因组序列替换策略主要分为2种:第1种依赖DNA双链断裂,包括将CRISPR-Cas分别与同... 利用基因组编辑技术可以对微生物、动植物和人类细胞系基因组进行精准的序列替换,加速生物育种进程和遗传性疾病治疗,从而在农业生产和医疗上取得突破。基因组序列替换策略主要分为2种:第1种依赖DNA双链断裂,包括将CRISPR-Cas分别与同源重组、单链退火、微同源末端连接等DNA修复途径相结合,或由位点特异性重组系统介导,实现精准的序列替换;第2种依赖DNA单链断裂,主要包括引导编辑、碱基编辑器等技术。本研究综述了不同精准序列替换策略和技术及相关研究进展,理清各策略和技术的优缺点,有助于根据基因组编辑的目的,选择适合的技术和方法实现精准高效的序列替换。 展开更多
关键词 基因组编辑 序列替换 DNA双链断裂 DNA单链断裂 DNA修复
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MRE11-RAD50-NBS1复合物的功能与人类疾病的研究进展
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作者 许晓慧 刘一丹 《中国医学科学院学报》 CAS CSCD 北大核心 2024年第2期232-241,共10页
生物体的DNA常遭受着来自体外和体内各种因素的攻击,其中DNA双链断裂(DSB)是严重的一种DNA损伤方式。为了保证遗传信息的稳定性,生物体自身存在应对DNA损伤的修复机制。同源重组修复是精确的修复DSB的方式,MRE11-RAD50-NBS1(MRN)复合物... 生物体的DNA常遭受着来自体外和体内各种因素的攻击,其中DNA双链断裂(DSB)是严重的一种DNA损伤方式。为了保证遗传信息的稳定性,生物体自身存在应对DNA损伤的修复机制。同源重组修复是精确的修复DSB的方式,MRE11-RAD50-NBS1(MRN)复合物是参与同源重组修复的关键蛋白,在不同物种之间存在保守性。从前关于MRN复合物的功能研究主要来源于酿酒酵母和线虫等低等生物,近些年来对哺乳动物MRN复合物的研究提示MRN复合物在高等动物DNA损伤修复中存在功能。本文综述了MRN复合物的组成和结构及其在DNA损伤同源重组修复中的功能,同时也介绍了MRN复合物异常所带来的人类疾病共济失调性毛细血管扩张综合征类似病症、奈梅亨断裂综合征和奈梅亨断裂综合征类似病症,并对这3类DNA损伤修复缺陷疾病的临床表型和相关小鼠模型研究进行了总结。 展开更多
关键词 DNA损伤修复 DNA双链断裂 同源重组 MRE11-RAD50-NBS1复合物
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川芎嗪通过RAD52调控乳腺癌细胞DNA损伤修复
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作者 黄溥婉 陈思龙 +2 位作者 唐喜军 伍湘峰 李莉萍 《现代肿瘤医学》 CAS 2024年第1期47-52,共6页
目的:探究TMP对乳腺癌BT474细胞增殖、细胞周期及其调控蛋白表达与DNA双链断裂修复通路的相关性。方法:CCK8法测定TMP对乳腺癌BT474细胞的增殖抑制情况;流式细胞术测定TMP对细胞周期的影响;单细胞凝胶电泳测定分析TMP对损伤后细胞DSBs... 目的:探究TMP对乳腺癌BT474细胞增殖、细胞周期及其调控蛋白表达与DNA双链断裂修复通路的相关性。方法:CCK8法测定TMP对乳腺癌BT474细胞的增殖抑制情况;流式细胞术测定TMP对细胞周期的影响;单细胞凝胶电泳测定分析TMP对损伤后细胞DSBs累积情况的影响;Isce-I内切酶系统检测TMP对修复通路活性的影响;Western blotting检测DSBs修复通路相关染色体结合蛋白表达水平变化。结果:TMP通过使细胞阻滞在G_(1)期呈浓度依赖性抑制BT474细胞增殖,显著减少体内由Zeocin导致的细胞拖尾DNA含量(P<0.05);TMP显著增加BT474细胞对RAD52、ERCC1、XRCC4以及DNA LigⅣ蛋白募集,减少对KU80蛋白募集,促进了SSA以及NHEJ通路修复活性(P<0.05)。结论:TMP通过阻滞BT474细胞停留在G_(1)期使其发挥增殖抑制作用的机制之一;TMP通过增强损伤缺口对各个通路的关键染色体结合蛋白募集,促进SSA与NHEJ修复通路活性从而减少DNA损伤。 展开更多
关键词 DNA双链断裂修复 川芎嗪 乳腺癌细胞
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与真核生物DSBs修复有关的NHEJ途径研究进展 被引量:3
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作者 虞海燕 梁锋 杨志伟 《生物技术通报》 CAS CSCD 北大核心 2009年第10期55-59,共5页
DNA双链断裂是真核生物最严重的DNA损伤形式。如果断裂的DNA双链无法及时修复,将可能导致细胞死亡。非同源末端连接途径在真核生物DSBs修复中起重要作用。综述了真核生物NHEJ途径中核心蛋白质Ku、DNA-PKcs、DNA连接酶IV、XRCC4、ARTEMIS... DNA双链断裂是真核生物最严重的DNA损伤形式。如果断裂的DNA双链无法及时修复,将可能导致细胞死亡。非同源末端连接途径在真核生物DSBs修复中起重要作用。综述了真核生物NHEJ途径中核心蛋白质Ku、DNA-PKcs、DNA连接酶IV、XRCC4、ARTEMIS和XIF等因子的结构和功能,并简要介绍了NHEJ修复途径的分子机制,其中涉及到DSBs位点蛋白复合体组装的两种模型。 展开更多
关键词 DNA双链断裂(dsbs) 非同源重组连接 KU蛋白
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基于DSBs修复蛋白表达构建预测食管鳞癌放化疗预后的列线图模型 被引量:6
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作者 刘维 高辉 +2 位作者 李华 李东 张涛 《实用医学杂志》 CAS 北大核心 2020年第8期1041-1047,共7页
目的探讨DNA双链断裂(DSBs)修复蛋白ATM、DNA-PKcs及P16表达水平与根治性放化疗食管鳞癌患者远期生存的关系,并建立列线图预测模型。方法收集2012-2017年收治的283例根治性放化疗食管鳞癌病例,按2:1随机分为建模组和验证组。免疫组化检... 目的探讨DNA双链断裂(DSBs)修复蛋白ATM、DNA-PKcs及P16表达水平与根治性放化疗食管鳞癌患者远期生存的关系,并建立列线图预测模型。方法收集2012-2017年收治的283例根治性放化疗食管鳞癌病例,按2:1随机分为建模组和验证组。免疫组化检测DSBs修复蛋白在肿瘤中的表达,Kaplan-Meier法计算生存率,Log-rank法进行单因素分析,Cox模型进行多因素分析,R软件构建列线图模型并进行内外部验证。结果建模组患者中位随访34个月,3、5年总生存率为35.1%和20.0%。多因素分析显示,ATM、DNA-PKcs或P16的表达与否,以及T、N分期均是患者OS的预后因素。建立列线图模型,预测建模组患者3、5年OS的一致性指数C-index为0.724,显著高于第七版AJCC临床分期的0.533(P <0.001)。对验证组患者进行验证,本模型和AJCC分期的C-index分别为0.792和0.550(P <0.001),均提示本模型比AJCC分期准确性更高。结论基于DSBs修复蛋白表达建立的列线图模型能较好地预测根治性放化疗食管鳞癌患者的远期生存,对指导个体化治疗有一定的临床意义。 展开更多
关键词 食管鳞癌 放化疗 dsbs修复蛋白 预后 列线图
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Rad51 ATP binding but not hydrolysis is required to recruit Rad10 in synthesis-dependent strand annealing sites in <i>S. cerevisiae</i>
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作者 Justin Karlin Paula L. Fischhaber 《Advances in Biological Chemistry》 2013年第3期295-303,共9页
Several modes of eukaryotic of DNA double strand break repair (DSBR) depend on synapsis of complementary DNA. The Rad51 ATPase, the S. cerevisiae homolog of E. coli RecA, plays a key role in this process by catalyzing... Several modes of eukaryotic of DNA double strand break repair (DSBR) depend on synapsis of complementary DNA. The Rad51 ATPase, the S. cerevisiae homolog of E. coli RecA, plays a key role in this process by catalyzing homology searching and strand exchange between an invading DNA strand and a repair template (e.g. sister chromatid or homologous chromosome). Synthesis dependent strand annealing (SDSA), a mode of DSBR, requires Rad51. Another repair enzyme, the Rad1-Rad10 endonuclease, acts in the final stages of SDSA, hydrolyzing 3¢ overhanging single-stranded DNA. Here we show in vivo by fluo-rescence microscopy that the ATP binding function of yeast Rad51 is required to recruit Rad10 SDSA sites indicating that Rad51 pre-synaptic filament formation must occur prior to the recruitment of Rad1-Rad10. Our data also show that Rad51 ATPase activity, an important step in Rad51 filament disassembly, is not absolutely required in order to recruit Rad1- Rad10 to DSB sites. 展开更多
关键词 Rad1 Rad10 RAD51 SYNTHESIS DEPENDENT strand ANNEALING Yeast double strand Break Repair
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木犀草素对人胃癌细胞DNA双链断裂及同源重组修复的影响 被引量:2
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作者 李冲慧 米阳 +4 位作者 任飞飞 孙向东 周潇潇 王万聪 夏兴洲 《胃肠病学和肝病学杂志》 CAS 2023年第4期385-391,共7页
目的探讨木犀草素对人胃癌细胞DNA双链断裂(DNA double-strand breaks,DSBs)及同源重组(homologous recombination,HR)修复的影响。方法采用流式细胞仪检测作用木犀草素后各组细胞内ROS水平变化及GFP阳性率;彗星实验检测木犀草素对DSBs... 目的探讨木犀草素对人胃癌细胞DNA双链断裂(DNA double-strand breaks,DSBs)及同源重组(homologous recombination,HR)修复的影响。方法采用流式细胞仪检测作用木犀草素后各组细胞内ROS水平变化及GFP阳性率;彗星实验检测木犀草素对DSBs的影响;Western blotting检测DNA损伤标志性蛋白γH2AX和HR修复蛋白Rad51的表达;免疫荧光检测DNA损伤修复相关蛋白表达的募集情况。结果木犀草素以剂量依赖性方式增加胃癌细胞内ROS含量;用I-Scel质粒转染DR-GFP后木犀草素处理组GFP阳性细胞比例明显少于未加木犀草素组;但彗星实验表明,木犀草素处理后人胃癌AGS细胞后增加彗星尾炬;经木犀草素处理后,胃癌细胞中DNA的γH2AX上调,修复关键蛋白Rad51的表达下调;免疫荧光结果表明,在木犀草素处理人胃癌AGS细胞后HR修复蛋白Rad51在DNA损伤位点的募集减少。结论木犀草素能够促进人胃癌细胞DSBs,并抑制其HR修复。 展开更多
关键词 木犀草素 DNA损伤 DNA双链断裂 同源重组修复 胃癌细胞
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基于机器学习方法对人类基因组DNA双链断裂位点进行识别
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作者 董碧宇 刘国庆 《中国生物化学与分子生物学报》 CAS CSCD 北大核心 2023年第8期1153-1167,共15页
DNA双链断裂(double-strand break,DSB)是细胞中一种严重的DNA损伤形式,与包括癌症、重组异常、神经元发育异常在内的多种基因组不稳定性疾病密切相关。由于成本和技术门槛的限制,高通量测序技术绘制的高分辨率DSB图谱十分有限,这阻碍... DNA双链断裂(double-strand break,DSB)是细胞中一种严重的DNA损伤形式,与包括癌症、重组异常、神经元发育异常在内的多种基因组不稳定性疾病密切相关。由于成本和技术门槛的限制,高通量测序技术绘制的高分辨率DSB图谱十分有限,这阻碍了我们对不同物种基因组中DSB情况的认知。据此,我们建立了以随机森林(RF)、支持向量机(SVM)和逻辑回归(LR)三种分类器为基础算法的分类预测模型,对人类上皮细胞基因组DSB位点进行预测。除了之前预测研究中常用到的表观特征和DNA形状特征外,我们发现DNA序列特征(k-mer频数、GC含量、GC-偏移和互信息)也能表征DSB位点。同时,在考虑DNA物理性质、化学位移和自相关信息后,预测结果得到有效提高。将上述所有特征合并后进行预测,得到了较好的分类预测结果,其中逻辑回归(LR)的分类预测性能是最佳(AUC=0.97),与以往的预测结果相当(AUC=0.964)。另外,通过特征递增搜索方法,得到由294个特征组成的最优特征集,对应的AUC值达到0.974。 展开更多
关键词 双链断裂 分类预测 化学位移 DNA物理性质 自相关
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CpG-ODN对重离子辐射所致脾脏损伤的救治作用
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作者 张超 傅华 +2 位作者 易永华 蔡建明 高福 《辐射研究与辐射工艺学报》 CAS CSCD 2023年第4期43-50,共8页
本次研究主要探讨CpG-ODN对重离子辐射所致脾脏损伤的救治作用。实验中C57BL/6L小鼠受到5 Gy12C6+离子全身照射,在照射后急性期计算小鼠脾脏指数,苏木精-伊红(Hematoxylin-Eosin staining,HE)染色观察脾脏组织结构变化。另外,免疫组化... 本次研究主要探讨CpG-ODN对重离子辐射所致脾脏损伤的救治作用。实验中C57BL/6L小鼠受到5 Gy12C6+离子全身照射,在照射后急性期计算小鼠脾脏指数,苏木精-伊红(Hematoxylin-Eosin staining,HE)染色观察脾脏组织结构变化。另外,免疫组化法检测γ-H2AX蛋白含量以判断脾脏细胞DNA发生双链断裂(Double-strand break,DSB)情况,末端脱氧核苷酸转移酶介导的dUTP缺口末端标(Terminal deoxynucleotidyl transferase-mediatedd UTPnickandlabeling,TUNEL)法检测脾脏细胞凋亡水平,荧光标记法检测外周血CD19+B细胞数量。结果显示,经12C6+离子照射后CpG-ODN处理,小鼠脾脏指数提高,脾脏红髓萎缩程度减轻,白髓面积增大,其内淋巴B细胞排列密度提高,发生DSB和凋亡的细胞数量减少,外周血CD19+B细胞数量增加。这些表明CpG-ODN能减轻12C6+离子照射后脾脏损伤,其原因可能与CpG-ODN抑制细胞发生DSB和凋亡有关。 展开更多
关键词 碳离子辐射 CPG-ODN 脾脏 凋亡 双链断裂
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DNA双链断裂修复缺陷在神经退行性疾病发生中的作用
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作者 接欣雨 唐铁山 刘红美 《生物医学转化》 2023年第2期31-41,共11页
DNA双链断裂修复(DNA Double-Strand Break Repair,DSBR)在保持神经元基因组稳定性和细胞存活方面发挥着重要作用。DSBR主要通过同源重组(Homologous Recombination,HR)及非同源末端连接(Non-Homologous End Joining,NHEJ)来完成,这两... DNA双链断裂修复(DNA Double-Strand Break Repair,DSBR)在保持神经元基因组稳定性和细胞存活方面发挥着重要作用。DSBR主要通过同源重组(Homologous Recombination,HR)及非同源末端连接(Non-Homologous End Joining,NHEJ)来完成,这两种修复途径对于维持神经元的正常生理功能至关重要。另外,DSBR异常在多种神经退行性疾病中扮演重要角色,因此,深入剖析DSBR机制对于理解神经退行性疾病的病理发生及研发有效治疗手段具有重要意义。本文综述了常见的DSBR途径,并概述了DSBR异常与几种常见神经退行性疾病发病机制的最新研究进展。 展开更多
关键词 DNA双链断裂修复 同源重组 非同源末端连接 神经退行性疾病
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组蛋白修饰调控53BP1与染色质结合功能的研究进展
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作者 陈思龙 黄溥婉 李莉萍 《南京医科大学学报(自然科学版)》 CAS 北大核心 2023年第1期113-121,共9页
p53结合蛋白1(p53-binding protein 1,53BP1)在协调DNA双链断裂(DNA double strand break,DSB)修复途径选择中起关键作用。关于53BP1募集到受损染色质中的基本分子机制,以及组蛋白修饰在53BP1募集中的作用,已有大量文献报道了全新的见解... p53结合蛋白1(p53-binding protein 1,53BP1)在协调DNA双链断裂(DNA double strand break,DSB)修复途径选择中起关键作用。关于53BP1募集到受损染色质中的基本分子机制,以及组蛋白修饰在53BP1募集中的作用,已有大量文献报道了全新的见解。H4K20me2和H2AK15ub是决定53BP1能否结合到受损染色质中的关键因素。最新证据表明,H3K18、H3K56乙酰化及H4K16乙酰化/甲基化对53BP1募集均有一定程度的影响。文章对53BP1的结构、53BP1募集的分子机制和组蛋白修饰在调节53BP1募集中的作用进行了综述,并为癌症治疗提供新的思路。 展开更多
关键词 p53结合蛋白1 组蛋白修饰 DNA双链断裂
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miR-34s增强结直肠癌细胞对放射敏感性的作用研究
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作者 陈双景 高琪琛 +4 位作者 曾浩 王军 朱征 刘波 苏璞 《现代肿瘤医学》 CAS 北大核心 2023年第14期2588-2592,共5页
目的:探讨miR-34s对结直肠癌细胞放射敏感性的影响以及在电离辐射致DNA损伤中的作用。方法:利用实时荧光定量PCR(real-time quantitative fluorescence PCR,qRT-PCR)检测miR-34a/b/c-5p在结直肠癌细胞中的表达水平,以及电离辐射后miR-34... 目的:探讨miR-34s对结直肠癌细胞放射敏感性的影响以及在电离辐射致DNA损伤中的作用。方法:利用实时荧光定量PCR(real-time quantitative fluorescence PCR,qRT-PCR)检测miR-34a/b/c-5p在结直肠癌细胞中的表达水平,以及电离辐射后miR-34a/b/c-5p表达水平变化趋势。基于克隆形成法和单击多靶模型建立细胞存活曲线,分析miR-34a/b/c-5p对结直肠癌细胞放射敏感性的影响。过表达miR-34a/b/c-5p并进行照射,利用免疫荧光法检测照射后γH2AX焦点形成情况,进而分析miR-34a/b/c-5p对电离辐射致DNA损伤的作用。结果:miR-34a/b/c-5p在HCT116细胞中的表达水平明显高于HT29细胞(P<0.05)。HCT116细胞经4 Gy照射后24 h内,miR-34a/b/c-5p表达水平呈双峰变化趋势。与miR-NC组相比,过表达miR-34a/b/c-5p可显著增加结直肠癌细胞的放射敏感性,miR-34a/b/c-5p组细胞平均致死剂量(D_(0))和准阈值剂量(D_(q))均明显降低,且辐射增敏比(SER)明显增加。过表达miR-34a/b/c-5p可显著增加电离辐射诱导的DNA双链断裂(double strand breaks,DSBs)水平,照射后1 h和8 hγH2AX焦点数明显高于miR-NC组(P<0.05)。结论:miR-34s为放射响应miRNA分子,过表达miR-34s可增加电离辐射诱导的DNA损伤水平并增强结直肠癌细胞的放射敏感性。 展开更多
关键词 结直肠癌 放射敏感性 miR-34s DNA双链断裂
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