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The role of PARP1 in the DNA damage response and its application in tumor therapy

null

《医学前沿（英文）》 2012年 第6卷 第2期   页码 156-164 doi: 10.1007/s11684-012-0197-3

摘要：

Single-strand break repair protein poly(ADP-ribose) polymerase 1 (PARP1) catalyzes the poly(ADP-ribosyl)ation of many key proteins in vivo and thus plays important roles in multiple DNA damage response pathways, rendering it a promising target in cancer therapy. The tumor-suppressor effects of PARP inhibitors have attracted significant interest for development of novel cancer therapies. However, recent evidence indicated that the underlying mechanism of PARP inhibitors in tumor therapy is more complex than previously expected. The present review will focus on recent progress on the role of PARP1 in the DNA damage response and PARP inhibitors in cancer therapy. The emerging resistance of BRCA-deficient tumors to PARP inhibitors is also briefly discussed from the perspective of DNA damage and repair. These recent research advances will inform the selection of patient populations who can benefit from the PARP inhibitor treatment and development of effective drug combination strategies.

关键词： PARP1     synthetic lethality     PARP inhibitor     DNA repair     cancer     NHEJ    

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Regulation and function of histone acetyltransferase MOF

null

《医学前沿（英文）》 2014年 第8卷 第1期   页码 79-83 doi: 10.1007/s11684-014-0314-6

摘要：

The mammalian MOF (male absent on the first), a member of the MYST (MOZ, YBF2, SAS2, and Tip60) family of histone acetyltransferases (HATs), is the major enzyme that catalyzes the acetylation of histone H4 on lysine 16. Acetylation of K16 is a prevalent mark associated with chromatin decondensation. MOF has recently been shown to play an essential role in maintaining normal cell functions. In this study, we discuss the important roles of MOF in DNA damage repair, apoptosis, and tumorigenesis. We also analyze the role of MOF as a key regulator of the core transcriptional network of embryonic stem cells.

关键词： MOF     histone acetyltransferase     DNA damage repair     tumorigenesis     embryonic stem cells    

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Generation and repair of AID-initiated DNA lesions in B lymphocytes

null

《医学前沿（英文）》 2014年 第8卷 第2期   页码 201-216 doi: 10.1007/s11684-014-0324-4

摘要：

Activation-induced deaminase (AID) initiates the secondary antibody diversification process in B lymphocytes. In mammalian B cells, this process includes somatic hypermutation (SHM) and class switch recombination (CSR), both of which require AID. AID induces U:G mismatch lesions in DNA that are subsequently converted into point mutations or DNA double stranded breaks during SHM/CSR. In a physiological context, AID targets immunoglobulin (Ig) loci to mediate SHM/CSR. However, recent studies reveal genome-wide access of AID to numerous non-Ig loci. Thus, AID poses a threat to the genome of B cells if AID-initiated DNA lesions cannot be properly repaired. In this review, we focus on the molecular mechanisms that regulate the specificity of AID targeting and the repair pathways responsible for processing AID-initiated DNA lesions.

关键词： class switch recombination     somatic hypermutation     activation-induced deaminase     DNA repair     genomic instability    

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Bacterial inactivation, DNA damage, and faster ATP degradation induced by ultraviolet disinfection

Chao Yang, Wenjun Sun, Xiuwei Ao

《环境科学与工程前沿（英文）》 2020年 第14卷 第1期 doi: 10.1007/s11783-019-1192-6

摘要： • Long amplicon is more effective to test DNA damage induced by UV. • ATP in bacteria does not degrade instantly but does eventually after UV exposure. • After medium pressure UV exposure, ATP degraded faster. The efficacy of ultraviolet (UV) disinfection has been validated in numerous studies by using culture-based methods. However, the discovery of viable but non-culturable bacteria has necessitated the investigation of UV disinfection based on bacterial viability parameters. We used quantitative polymerase chain reaction (qPCR) to investigate DNA damage and evaluated adenosine triphosphate (ATP) to indicate bacterial viability. The results of qPCR effectively showed the DNA damage induced by UV when using longer gene amplicons, in that sufficiently long amplicons of both 16S and gadA indicated that the UV induced DNA damages. The copy concentrations of the long amplicons of 16S and gadA decreased by 2.38 log/mL and 1.88 log/mL, respectively, after exposure to 40 mJ/cm2 low-pressure UV. After UV exposure, the ATP level in the bacteria did not decrease instantly. Instead it decreased gradually at a rate that was positively related to the UV fluence. For low-pressure UV, this rate of decrease was slow, but for medium pressure UV, this rate of decrease was relatively high when the UV fluence reached 40 mJ/cm2. At the same UV fluence, the ATP level in the bacteria decreased at a faster rate after exposure to medium-pressure UV.

关键词： UV disinfection     DNA damage     qPCR     ATP    

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Effects of DNA damage on oocyte meiotic maturation and early embryonic development

Shen YIN,Junyu MA,Wei SHEN

《农业科学与工程前沿（英文）》 2014年 第1卷 第3期   页码 185-190 doi: 10.15302/J-FASE-2014035

摘要： DNA damage is one of the most common threats to meiotic cells. It has the potential to induce infertility and genetic abnormalities that may be passed to the embryo. Here, we reviewed exogenous factors which could induce DNA damage. Specially, we addressed the different effects of DNA damage on mouse oocytes and embryonic development. Complex DNA damage, double-strand breaks, represents a more difficult repair process and involves various repair pathways. Understanding the mechanisms involved in DNA damage responses may improve therapeutic strategies for ovarian cancer and fertility preservation.

关键词： DNA damage     double-strand breaks (DSBs)     oocyte     embryo    

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hydrophobic environment triggering reactive fluorescence probe to real-time monitor mitochondrial DNAdamage

《化学科学与工程前沿（英文）》 2022年 第16卷 第1期   页码 92-102 doi: 10.1007/s11705-021-2063-9

摘要： Mitochondrial DNA has a special structure that is prone to damage resulting in many serious diseases, such as genetic diseases and cancers. Therefore, the rapid and specific monitoring of mitochondrial DNA damage is urgently needed for biological recognition. Herein, we constructed an in situ hydrophobic environment-triggering reactive fluorescence probe named MBI-CN. The fluorophore was 2-styrene-1H-benzo[d]imidazole, and malononitrile was introduced as a core into a molecule to initiate the hydrolysis reaction in the specific environment containing damaged mitochondrial DNA. In this design, MBI-CN conjugates to mitochondrial DNA without causing additional damages. Thus, MBI-CN can be hydrolyzed to generate MBI-CHO in an in situ hydrophobic environment with mitochondrial DNA damage. Meanwhile, MBI-CHO immediately emitted a significative fluorescence signal changes at 437 and 553 nm within 25 s for the damaged mitochondria DNA. Give that the specific and rapid response of MBI-CN does not cause additional damages to mitochondrial DNA, it is a potentially effective detection tool for the real-time monitoring of mitochondrial DNA damage during cell apoptosis and initial assessment of cell apoptosis.

关键词： hydrolysis reaction     mitochondrial DNA damage     in situ hydrophobic environment trigger     fluorescence probe     apoptosis    

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Detection of oxidative stress and DNA damage in freshwater snail

Daoud Ali, Huma Ali, Saud Alifiri, Saad Alkahtani, Abdullah A Alkahtane, Shaik Althaf Huasain

《环境科学与工程前沿（英文）》 2018年 第12卷 第5期 doi: 10.1007/s11783-018-1039-6

摘要：

Freshwater snail (Lymnea luteola L.) is good bio indicator of water pollution.

Profenofos is tested for its molluscicidal activity against Lymnea luteola L. snail.

Deleterious effects on some oxidative stress were detected.

Profenofos has a genotoxic effect on Lymnea luteola L. snails.

关键词： Acute toxicity     Profenofos     ROS     oxidative stress     DNA damage     Lymnea luteola    

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Correlativity study between expression of DNA double-strand break repair protein and radiosensitivity

Liang ZHUANG, Shiying YU, Xiaoyuan HUANG, Yang CAO, Huihua XIONG

《医学前沿（英文）》 2009年 第3卷 第1期   页码 26-29 doi: 10.1007/s11684-009-0008-7

摘要： DNA double-strand break (DSB) is generally regarded as the most lethal of all DNA lesions after radiation. Ku80, DNA-PK catalytic subunit (DNA-PKcs) and ataxia telangiectasia mutated (ATM) proteins are major DSB repair proteins. In this study, survival fraction at 2Gy (SF2) values of eight human tumor cell lines (including four human cervical carcinoma cell lines HeLa, SiHa, C33A, Caski, three human breast carcinoma cell lines MCF-7, MDA-MB-231, MDA-MB-453, and one human lung carcinoma cell line A549) were acquired by clone formation assay, and western blot was applied to detect the expressions of Ku80, DNA-PKcs and ATM protein. The correlativity of protein expression with SF2 value was analyzed by Pearson linear correlation analysis. We found that the expression of same protein in different cell lines and the expression of three proteins in the same cell line had a significant difference. The SF2 values were also different in eight tumor cell lines and there was a positive correlativity between the expression of DNA-PKcs and SF2 ( ＝0.723, = 0.043), but Ku80 and ATM expression had no correlation with SF2 ( >0.05). These findings suggest that the expression level of DNA-PKcs protein can be an indicator for predicting the radiosensitivity of tumor cells.

关键词： Ku80     DNA-PK(cs)-binding protein     human     ataxia telangiectasia mutated protein     tumor cell lines     radiosensitivity    

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Functional role of ATM in the cellular response to DNA damage

Ming LIU, Wenxiang HU

《化学科学与工程前沿（英文）》 2011年 第5卷 第2期   页码 179-187 doi: 10.1007/s11705-009-0268-4

摘要： Ataxia-telangiectasia mutated (ATM) plays a key role in regulating the cellular response to ionizing radiation. The tumor-suppressor gene ATM, mutations in which cause the human genetic disease ataxia telangiectasia, encodes a key protein kinase that controls the cellular response to double-stranded breaks. Activation of ATM results in phosphorylation of many downstream targets that modulate numerous damage response pathways, most notably cell cycle checkpoints. Here, we highlight some of the new developments in the field in our understanding of the mechanism of activation of ATM and its signaling pathways, explore whether DNA double-strand breaks are the sole activators of ATM and ATM-dependent signaling pathways, and address some of the prominent, unanswered questions related to ATM and its function. The scope of this article is to provide a brief overview of the recent literature on this subject and to raise questions that could be addressed in future studies.

关键词： ataxia-telangiectasia mutated (ATM)     cell cycle checkpoint     DNA damage     signalling transduction    

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Relationship between reactive oxygen species and sodium-selenite-induced DNA damage in HepG2 cells

ZOU Yunfeng, NIU Piye, GONG Zhiyong, YANG Jin, YUAN Jing, WU Tangchun, CHEN Xuemin

《医学前沿（英文）》 2007年 第1卷 第3期   页码 327-332 doi: 10.1007/s11684-007-0063-x

摘要： Selenium compounds, as an effective chemopreventive agent, can induce apoptosis in tumor cells. Reactive oxygen species (ROS) are important mediators in apoptosis induced by various stimuli, which include chemopreventive agents. In this study, we investigated the relationship between ROS and the levels of DNA damage induced by selenite in HepG2 cells. After HepG2 cells were treated with selenite, there was a dose-dependent decrease in cell viability. The levels of ROS induced by selenite were measured by 2′, 7′-dichlorofluorescein diacetate (DCFH-DA) fluorescence, which shows a dose- and time-dependent increase in HepG2 cells. The levels of DNA damage in HepG2 increased in all cells treated with an increasing dose of selenite at 0, 2.5, 5, 10, and 20 μmol/L. N-acetylcysteine (NAC), a known antioxidant, increased cell viability and decreased ROS generation. Moreover, NAC effectively blocked DNA damage induced by selenite. These results revealed that ROS might play an important role in selenite-induced DNA damage that can be reduced by NAC treatment.

关键词： NAC     N-acetylcysteine     DNA     fluorescence     relationship    

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Bile duct injury repair — earlier is not better

null

《医学前沿（英文）》 2015年 第9卷 第4期   页码 508-511 doi: 10.1007/s11684-015-0418-7

摘要：

Bile duct injury is a common complication of cholecystectomy. The timing of bile duct injury repair remains controversial. A recent review conducted in France reported 39% complications and 64% failure after immediate repair in 194 patients compared with 14% complications and 8% failure after late repair in 133 patients. A national review of 139 consecutive early repairs conducted at five hepatopancreaticobiliary centers in Denmark reported 4% mortality, 36% morbidity, and 42 restrictures (30%) at a median follow-up of 102 months, and only 64 patients (46%) demonstrated uneventful short-term and long-term outcomes. Most patients with bile duct injury present with bile leak and sepsis; thus, early repair is not recommended. Percutaneous drainage of bile and endoscopic stenting are the mainstays of treatment of bile leak because they convert acute bile duct injury into a controlled external biliary fistula. The ensuing benign biliary stricture should be repaired by a biliary surgeon after a delay of 4–6 weeks once the external biliary fistula has closed.

关键词： bile duct injury     cholecystectomy     laparoscopic cholecystectomy    

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p53 functional activation is independent of its genotype in five esophageal squamous cell carcinoma cell lines

Junfang JI, Kun WU, Min WU, Qimin ZHAN,

《医学前沿（英文）》 2010年 第4卷 第4期   页码 412-418 doi: 10.1007/s11684-010-0260-x

摘要： mutations have been found in many esophageal squamous cell carcinoma (ESCC) clinical specimens and cell lines. We reasoned that functional inactivation of wild-type or the functional activation of mutant-type might exist in these specimens and cell lines. In this study, we identified the correlation between p53 functional activation and its genotype in five different ESCC cell lines. To examine the potential p53 activation in a certain ESCC cell line, DNA damage methods including X-ray exposure and cisplatin treatment were employed to treat cells. Further, the expression of p53 protein and four transcripts of well-known p53 target genes were investigated using Western blot and reverse transcription-polymerase chain reaction (RT-PCR) after cell exposure to DNA damage. The results showed that in KYSE 30 cell line with mutant and KYSE 150 with wild-type , p53 could be activated by DNA damages. However, p53 could not be activated following the DNA damages in YES 2 with wild-type , KYSE 70 with mutant , and EC9706 with unknown genotype. All our data indicated that p53 function in certain cells is not closely correlated with its genotype. To judge p53 function in a particular cell line, it is important to examine the p53 functional activation, but not to simply rely on the genotype.

关键词： p53     esophageal squamous cell carcinoma     DNA damage    

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工程化DNA材料构建DNA活字系统实现可持续的数据存储 Article

巩子祎, 宋理富, 裴广胜, 董雨菲, 李炳志, 元英进

《工程（英文）》 2023年 第29卷 第10期   页码 130-136 doi: 10.1016/j.eng.2022.05.023

摘要：

DNA分子作为一种具有潜力的数据存储绿色材料，具有密度高和保存期长的优势。然而，目前DNA数据存储的数据写入依赖于DNA从头合成，写入成本高昂，且产生有害物，限制了其实际应用。在本研究中，我们开发了一种DNA活字存储系统，该系统可以利用由细胞工厂预生产的DNA活字片段进行数据写入。在这个系统中，这些预先生成的DNA片段，在这里称为“DNA活字”，是可重复使用的基本数据单元。通过这些DNA活字的快速组装来实现数据写入，从而避免了昂贵且对环境有害的DNA化学合成过程。通过DNA活字片段的反复使用和生物组装，该系统在降低写入成本方面的潜力非常突出，为经济和可持续的DNA数据存储技术开辟了一条新颖路线。

关键词： 合成生物学     DNA信息存储     DNA活字存储系统     经济性DNA数据存储    

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Mobile platform for hydraulic turbine blade repair robot

GUI Zhongcheng, CHEN Qiang, SUN Zhenguo, ZHANG Wenzeng, LIU Kang

《机械工程前沿（英文）》 2008年 第3卷 第2期   页码 164-169 doi: 10.1007/s11465-008-0035-0

摘要： The wall-climbing mobile platform (MP) of a robot for repairing a hydraulic turbine blade onsite is developed. The MP is equipped with ferromagnetic adhesive devices and can work on a spatial curved surface. The contradiction between mobility and load-bearing ability is analyzed, and the problem of self-adaptation to the curved face is solved using differential-driven wheeled locomotion with ferromagnetic adhesive devices. The platform adheres to the blade surface through the force provided by the ferromagnetic devices, and a certain gap exists between the magnetic devices and the blade’s surface. A mechanism of three revolution degrees of freedom, which connects the magnetic devices with the platform’s chassis, is developed to make the platform self-adapt to the complex curved surface of the turbine blade. A proof-of-principle prototype has been manufactured, and experiments prove the success of the MP. The payload of the zero-turn-radius MP with excellent maneuverability exceeds 80 kg. The platform can automatically adapt to complex spatial surfaces, which satisfy the requirements of a hydraulic turbine blade in-situ repair robot.
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Expression status of GATA3 and mismatch repair proteins in upper tract urothelial carcinoma

Yue Wang, Jinxia Zhang, Yunfan Wang, Shufang Wang, Yu Zhang, Qi Miao, Fei Gao, Huiying He

《医学前沿（英文）》 2019年 第13卷 第6期   页码 730-740 doi: 10.1007/s11684-019-0687-7

摘要： GATA binding protein 3 (GATA3) and mismatch repair (MMR) deficiency contribute to the development of urothelial carcinoma. However, the combined expression of GATA3 and microsatellite instability (MSI) in upper tract urothelial carcinoma (UTUC) and its prognostic value have not been investigated. Here, we immunohistochemically stained GATA3 and MMR proteins in 108 UTUC samples. GATA3 was positive in 74 cases, and its expression was significantly lower than in adjacent benign urothelium ( <0.001). Loss of GATA3 expression was statistically associated with adverse clinicopathologic parameters, such as advanced stage, lymphovascular invasion, neural invasion, lymph node metastasis, and extensive necrosis. Cancer-specific survival (CSS, =0.028) and disease-free survival (DFS, =0.024) were significantly shorter in patients with GATA3 negative tumors than in patients with GATA3 positive tumors. The absence of MMR proteins was observed in 8.3% of the cases, and focal staining was identified in 13.0%. When using “lax criteria” which resulted in counting cases as negative where MMR staining was in fact focally positive (<5%), we found that GATA3 was inversely associated with MSI ( =0.005). Moreover, GATA3 /microsatellite stability (MS) tumors were correlated with advanced pT stage ( <0.001) and poor outcome ( =0.019 for CSS, =0.016 for DFS) compared with GATA3 /MSI ones. The GATA3 /MSI cases had unfavorable clinical outcomes compared with GATA3 /MSI cases ( =0.008 for CSS, =0.023 for DFS). This finding raises a question as to whether GATA3 interacts with MSI through the TGF- signaling pathway and regulates UTUC progression.

关键词： upper tract urothelial carcinoma     GATA binding protein 3     mismatch repair     microsatellite instability     prognosis    

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标题 作者 时间 类型 操作

The role of PARP1 in the DNA damage response and its application in tumor therapy

null

期刊论文

Regulation and function of histone acetyltransferase MOF

null

期刊论文

Generation and repair of AID-initiated DNA lesions in B lymphocytes

null

期刊论文

Bacterial inactivation, DNA damage, and faster ATP degradation induced by ultraviolet disinfection

Chao Yang, Wenjun Sun, Xiuwei Ao

期刊论文

Effects of DNA damage on oocyte meiotic maturation and early embryonic development

Shen YIN,Junyu MA,Wei SHEN

期刊论文

hydrophobic environment triggering reactive fluorescence probe to real-time monitor mitochondrial DNAdamage

期刊论文

Detection of oxidative stress and DNA damage in freshwater snail

Daoud Ali, Huma Ali, Saud Alifiri, Saad Alkahtani, Abdullah A Alkahtane, Shaik Althaf Huasain

期刊论文

Correlativity study between expression of DNA double-strand break repair protein and radiosensitivity

Liang ZHUANG, Shiying YU, Xiaoyuan HUANG, Yang CAO, Huihua XIONG

期刊论文

Functional role of ATM in the cellular response to DNA damage

Ming LIU, Wenxiang HU

期刊论文

Relationship between reactive oxygen species and sodium-selenite-induced DNA damage in HepG2 cells

ZOU Yunfeng, NIU Piye, GONG Zhiyong, YANG Jin, YUAN Jing, WU Tangchun, CHEN Xuemin

期刊论文

Bile duct injury repair — earlier is not better

null

期刊论文

p53 functional activation is independent of its genotype in five esophageal squamous cell carcinoma cell lines

Junfang JI, Kun WU, Min WU, Qimin ZHAN,

期刊论文

工程化DNA材料构建DNA活字系统实现可持续的数据存储

巩子祎, 宋理富, 裴广胜, 董雨菲, 李炳志, 元英进

期刊论文

Mobile platform for hydraulic turbine blade repair robot

GUI Zhongcheng, CHEN Qiang, SUN Zhenguo, ZHANG Wenzeng, LIU Kang

期刊论文

Expression status of GATA3 and mismatch repair proteins in upper tract urothelial carcinoma

Yue Wang, Jinxia Zhang, Yunfan Wang, Shufang Wang, Yu Zhang, Qi Miao, Fei Gao, Huiying He

期刊论文