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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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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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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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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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Bile duct injury repair — earlier is not better

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《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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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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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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Molecular simulation of the interaction mechanism between CodY protein and DNA in

Linchen Yuan, Hao Wu, Yue Zhao, Xiaoyu Qin, Yanni Li

《化学科学与工程前沿（英文）》 2019年第13卷第1期页码 133-139 doi: 10.1007/s11705-018-1737-4

摘要： In , the global transcriptional regulatory factor CodY can interact with the promoter DNA to regulate the growth, metabolism, environmental adaptation and other biological activities of the strains. In order to study the mechanism of interaction between CodY and its target DNA, molecular docking and molecular dynamics simulations were used to explore the binding process at molecular level. Through the calculations of the free energy of binding, hydrogen bonding and energy decomposition, nine key residues of CodY were identified, corresponding to SER184, SER186, SER208, THR217, ARG218, SER219, ASN223, LYS242 and GLY243, among which SER186, ARG218 and LYS242 play a vital role in DNA binding. Our research results provide important theoretical guidance for using wet-lab methods to study and optimize the metabolic network regulated by CodY.

关键词： CodY DNA molecular docking molecular dynamics

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Environmental pollution and DNA methylation: carcinogenesis, clinical significance, and practical applications

null

《医学前沿（英文）》 2015年第9卷第3期页码 261-274 doi: 10.1007/s11684-015-0406-y

摘要：

Environmental pollution is one of the main causes of human cancer. Exposures to environmental carcinogens result in genetic and epigenetic alterations which induce cell transformation. Epigenetic changes caused by environmental pollution play important roles in the development and progression of environmental pollution-related cancers. Studies on DNA methylation are among the earliest and most conducted epigenetic research linked to cancer. In this review, the roles of DNA methylation in carcinogenesis and their significance in clinical medicine were summarized, and the effects of environmental pollutants, particularly air pollutants, on DNA methylation were introduced. Furthermore, prospective applications of DNA methylation to environmental pollution detection and cancer prevention were discussed.

关键词： environmental pollution DNA methylation cancer biomarker diagnosis therapy prevention

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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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表征不同DNA高阶结构的单分子分析方法 Review

刘泳麟, 边天元, 刘岩, 李治民, 裴羽丰, 宋杰

《工程（英文）》 2023年第24卷第5期页码 277-292 doi: 10.1016/j.eng.2022.10.009

摘要：

DNA不仅是生命遗传信息的载体，而且是一种高度可编程和自组装的纳米材料。不同的DNA结构与其生物学和化学功能有关。因此，了解各种DNA结构的物理和化学性质在生物学和纳米化学中具有重要意义。然而，群体分子实验忽略了溶液中DNA结构的异质性。单分子分析方法是观察单个分子的行为和探测自由能态的高异质性的有力工具。本文介绍了单分子检测和操纵等单分子分析方法，并讨论了这些方法如何用于测量单/双链DNA（ss/dsDNA）、DNA高阶结构和DNA纳米结构的分子性质。最后，将DNA纳米技术和单分子分析方法进行结合以了解DNA和其他生物物质、软物质的生物物理特性。

关键词：单分子分析方法 DNA结构力学性能构象转变

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Experimental study and field application of calcium sulfoaluminate cement for rapid repair of concrete

Yanhua GUAN, Ying GAO, Renjuan SUN, Moon C. WON, Zhi GE

《结构与土木工程前沿（英文）》 2017年第11卷第3期页码 338-345 doi: 10.1007/s11709-017-0411-0

摘要： The fast-track repair of deteriorated concrete pavement requires materials that can be placed, cured, and opened to the traffic in a short period. Type III cement and Calcium Sulfoaluminate (CSA) cement are the most commonly used fast-setting hydraulic cement (FSHC). In this study, the properties of Type III and CSA cement concrete, including compressive strength, coefficient of thermal expansion (CTE) and shrinkage were evaluated. The test results indicate that compressive strength of FSHC concrete increased rapidly at the early age. CSA cement concrete had higher early-age and long term strength. The shrinkage of CSA cement concrete was lower than that of Type III cement concrete. Both CSA and Type III cement concrete had similar CTE values. Based on the laboratory results, the CSA cement was selected as the partial-depth rapid repair material for a distressed continuously reinforced concrete pavement. The data collected during and after the repair show that the CSA cement concrete had good short-term and long-term performances and, therefore, was suitable for the rapid repair of concrete pavement.

关键词： Calcium Sulfoaluminate (CSA) cement Type III cement coefficient of thermal expansion (CTE) shrinkage rapid repair

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基于探针图的并行型图顶点着色DNA计算模型 Article

许进, 强小利, 张凯, 张成, 杨静

《工程（英文）》 2018年第4卷第1期页码 61-77 doi: 10.1016/j.eng.2018.02.011

摘要：

目前DNA 计算机研究中遇到的最大瓶颈是解空间指数爆炸问题，即随着问题规模的增大，所需要作为信息处理“数据”的DNA分子呈指数级增大。本文提出了一种新颖的图顶点着色DNA计算模型，该模型正是围绕着如何克服解空间指数爆炸问题以及如何提高运行速度而设计的。本文以一个3-着色的61 个顶点的图为例，实验表明，99% 的非可行解在构建初始解空间时就被删除，并利用DNA 自组装和并行PCR 方法，通过识别、拼接以及组装等技术得到解。

关键词： DNA计算图顶点着色问题聚合酶链反应（PCR）