Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis最新文献_第9页

Characterization and implementation of a miniature X-ray system for live cell microscopy 用于活细胞显微镜的微型x射线系统的特性和实现

IF 2.3 4区医学

Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis Pub Date : 2022-01-01 DOI: 10.1016/j.mrfmmm.2021.111772

Surendra Prajapati , Maëlle Locatelli , Caleb Sawyer , Julia Holmes , Keith Bonin , Paul Black , Pierre-Alexandre Vidi

{"title":"Characterization and implementation of a miniature X-ray system for live cell microscopy","authors":"Surendra Prajapati , Maëlle Locatelli , Caleb Sawyer , Julia Holmes , Keith Bonin , Paul Black , Pierre-Alexandre Vidi","doi":"10.1016/j.mrfmmm.2021.111772","DOIUrl":"10.1016/j.mrfmmm.2021.111772","url":null,"abstract":"<div>The study of radiation effects on biological tissues is a diverse field of research with direct applications to improve human health, in particular in the contexts of radiation therapy and space exploration. Understanding the DNA damage response following radiation exposure, which is a key determinant for mutagenesis, requires reproducible methods for delivering known doses of ionizing radiation (IR) in a controlled environment. Multiple IR sources, including research X-ray and gamma-ray irradiators are routinely used in basic and translational research with cell and animal models. These systems are however not ideal when a high temporal resolution is needed, for example to study early DNA damage responses with live cell microscopy. Here, we characterize the dose rate and beam properties of a commercial, miniature, affordable, and versatile X-ray source (Mini-X). We describe how to use Mini-X on the stage of a fluorescence microscope to deliver high IR dose rates (up to 29 Gy/min) or lower dose rates (≤ 0.1 Gy/min) in live cell imaging experiments. This article provides a blueprint for radiation biology applications with high temporal resolution, with a step-by-step guide to implement a miniature X-ray system on an imaging platform, and the information needed to characterize the system.</div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"824 ","pages":"Article 111772"},"PeriodicalIF":2.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39614416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Aneuploidy, inflammation and diseases 非整倍体，炎症和疾病

IF 2.3 4区医学

Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis Pub Date : 2022-01-01 DOI: 10.1016/j.mrfmmm.2022.111777

Micheline Kirsch-Volders , Michael Fenech

{"title":"Aneuploidy, inflammation and diseases","authors":"Micheline Kirsch-Volders , Michael Fenech","doi":"10.1016/j.mrfmmm.2022.111777","DOIUrl":"10.1016/j.mrfmmm.2022.111777","url":null,"abstract":"<div>This review discusses how numerical aneuploidy may trigger inflammation in somatic cells and its consequences. Therefore we: i) summarized current knowledge on the cellular and molecular pathological effects of aneuploidy; ii) considered which of these aspects are able to trigger inflammation; iii) determined the genetic and environmental factors which may modulate the link between aneuploidy and inflammation; iv) explored the rôle of diet in prevention of aneuploidy and inflammation; v) examined whether aneuploidy and inflammation are causes and/or consequences of diseases; vi) identified the knowledge gaps and research needed to translate these observations into improved health care and disease prevention.The relationships between aneuploidy, inflammation and diseases are complex, because they depend on which chromosomes are involved, the proportion of cells affected and which organs are aneuploid in the case of mosaic aneuploidy. Therefore, a systemic approach is recommended to understand the emergence of aneuploidy-driven diseases and to take preventive measures to protect individuals from exposure to aneugenic conditions.</div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"824 ","pages":"Article 111777"},"PeriodicalIF":2.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42155869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Novel plasmids for the fluorescence-based evaluation of DNA mismatch repair in human cells 荧光评价人类细胞DNA错配修复的新型质粒

IF 2.3 4区医学

Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis Pub Date : 2022-01-01 DOI: 10.1016/j.mrfmmm.2022.111779

Arato Takedachi , Erina Matsuishi , Shouji Mizusaki , Tomoki Nagasawa , Ryosuke Fujikane , Masumi Hidaka , Shigenori Iwai , Isao Kuraoka

{"title":"Novel plasmids for the fluorescence-based evaluation of DNA mismatch repair in human cells","authors":"Arato Takedachi , Erina Matsuishi , Shouji Mizusaki , Tomoki Nagasawa , Ryosuke Fujikane , Masumi Hidaka , Shigenori Iwai , Isao Kuraoka","doi":"10.1016/j.mrfmmm.2022.111779","DOIUrl":"10.1016/j.mrfmmm.2022.111779","url":null,"abstract":"<div>Mismatch repair (MMR) is a highly conserved DNA repair pathway that corrects mismatched bases during DNA replication. The biological significance of MMR in human cells is underscored by the fact that dysfunction of the MMR pathway results in Lynch syndrome, which is associated with a genetic predisposition to different cancer types. We have previously established a reporter mismatch plasmid to evaluate MMR using fluorescent proteins in living cells. However, the preparation of these plasmids requires significant amounts of time and money, which reduces their broad applicability. To overcome the abovementioned limitations, we produced in this study a novel reporter plasmid, pBSII NLS-MC-EGFP-tdTomato (pBET2), that can be used in the oligo swapping method. In this method, a nicking endonuclease produces a single-stranded DNA gap on a double-stranded DNA plasmid that can be replaced by ligation with synthetic oligonucleotides. It is significantly easier and more user-friendly than previous assays, which require in vitro DNA synthesis with single-stranded plasmid DNA and purification using ultracentrifugation in cesium chloride-ethidium bromide gradients. The plasmid also contains a nicking site that allows the MMR repair machinery to efficiently distinguish the newly synthesized strand as a target for repair. In addition, a nuclear localization signal facilitates green fluorescent protein expression in the nucleus, which helps to verify the effectiveness of MMR using fluorescence microscopy. Similar to the previous reporter plasmid, this construct facilitates the assessment of MMR proficiency in human living cells via the expression of fluorescent proteins while overcoming many of the negative aspects of the previous protocol.</div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"824 ","pages":"Article 111779"},"PeriodicalIF":2.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47791235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In vitro and in silico analysis of a E559K mutation on cartilage oligomeric matrix protein 软骨寡聚基质蛋白E559K突变的体外和计算机分析

IF 2.3 4区医学

Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis Pub Date : 2022-01-01 DOI: 10.1016/j.mrfmmm.2022.111774

Jiahui Qiu , Jichun Tan

引用次数: 0

Cell cycle involvement in cancer therapy; WEE1 kinase, a potential target as therapeutic strategy 细胞周期参与癌症治疗;WEE1激酶，作为治疗策略的潜在靶点

IF 2.3 4区医学

Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis Pub Date : 2022-01-01 DOI: 10.1016/j.mrfmmm.2022.111776

Sajjad Vakili-Samiani , Omid Joodi Khanghah , Elham Gholipour , Fatemeh Najafi , Elham Zeinalzadeh , Parisa Samadi , Parisa Sarvarian , Shiva Pourvahdani , Shohre Karimi Kelaye , Michael R. Hamblin , Abbas Ali Hosseinpour Feizi

{"title":"Cell cycle involvement in cancer therapy; WEE1 kinase, a potential target as therapeutic strategy","authors":"Sajjad Vakili-Samiani , Omid Joodi Khanghah , Elham Gholipour , Fatemeh Najafi , Elham Zeinalzadeh , Parisa Samadi , Parisa Sarvarian , Shiva Pourvahdani , Shohre Karimi Kelaye , Michael R. Hamblin , Abbas Ali Hosseinpour Feizi","doi":"10.1016/j.mrfmmm.2022.111776","DOIUrl":"10.1016/j.mrfmmm.2022.111776","url":null,"abstract":"<div>Mitosis is the process of cell division and is regulated by checkpoints in the cell cycle. G1-S, S, and G2-M are the three main checkpoints that prevent initiation of the next phase of the cell cycle phase until previous phase has completed. DNA damage leads to activation of the G2-M checkpoint, which can trigger a downstream DNA damage response (DDR) pathway to induce cell cycle arrest while the damage is repaired. If the DNA damage cannot be repaired, the replication stress response (RSR) pathway finally leads to cell death by apoptosis, in this case called mitotic catastrophe. Many cancer treatments (chemotherapy and radiotherapy) cause DNA damages based on SSBs (single strand breaks) or DSBs (double strand breaks), which cause cell death through mitotic catastrophe. However, damaged cells can activate WEE1 kinase (as a part of the DDR and RSR pathways), which prevents apoptosis and cell death by inducing cell cycle arrest at G2 phase. Therefore, inhibition of WEE1 kinase could sensitize cancer cells to chemotherapeutic drugs. This review focuses on the role of WEE1 kinase (as a biological macromolecule which has a molecular mass of 96 kDa) in the cell cycle, and its interactions with other regulatory pathways. In addition, we discuss the potential of WEE1 inhibition as a new therapeutic approach in the treatment of various cancers, such as melanoma, breast cancer, pancreatic cancer, cervical cancer, etc.</div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"824 ","pages":"Article 111776"},"PeriodicalIF":2.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42087612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

The Kidney-Expressed Transcription Factor Zkscan3 is Dispensable for Autophagy Transcriptional Regulation and Aki Progression in Mouse 肾脏表达的转录因子Zkscan3在小鼠自噬转录调控和Aki进展中是不可或缺的

IF 2.3 4区医学

Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis Pub Date : 2022-01-01 DOI: 10.2139/ssrn.4048743

Huafeng Liu, Ze-jian Liu, Xiaoyu Li, Xingyu Li, Zixian Li, Huixia Chen, S-Q Gong, Minjie Zhang, Yaozhi Zhang, Zhihang Li, Lin Yang

引用次数: 0

Distribution of copy number variations and rearrangement endpoints in human cancers with a review of literature 人类癌症中拷贝数变异和重排终点的分布与文献综述

IF 2.3 4区医学

Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis Pub Date : 2022-01-01 DOI: 10.1016/j.mrfmmm.2021.111773

Golrokh Mirzaei , Ruben C. Petreaca

引用次数: 6

Genome-wide profiles of UV lesion susceptibility, repair, and mutagenic potential in melanoma 黑色素瘤中紫外线损伤易感性、修复和致突变潜力的全基因组谱

IF 2.3 4区医学

Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis Pub Date : 2021-07-01 DOI: 10.1016/j.mrfmmm.2021.111758

Brian S. Perez, Ka Man Wong, Erin K. Schwartz , Rafael E. Herrera, Devin A. King, Pablo E. García-Nieto, Ashby J. Morrison

{"title":"Genome-wide profiles of UV lesion susceptibility, repair, and mutagenic potential in melanoma","authors":"Brian S. Perez, Ka Man Wong, Erin K. Schwartz , Rafael E. Herrera, Devin A. King, Pablo E. García-Nieto, Ashby J. Morrison","doi":"10.1016/j.mrfmmm.2021.111758","DOIUrl":"10.1016/j.mrfmmm.2021.111758","url":null,"abstract":"<div>Exposure to the ultraviolet (UV) radiation in sunlight creates DNA lesions, which if left unrepaired can induce mutations and contribute to skin cancer. The two most common UV-induced DNA lesions are the cis-syn cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs), both of which can initiate mutations. Interestingly, mutation frequency across the genomes of many cancers is heterogenous with significant increases in heterochromatin. Corresponding increases in UV lesion susceptibility and decreases in repair are observed in heterochromatin versus euchromatin. However, the individual contributions of CPDs and 6-4PPs to mutagenesis have not been systematically examined in specific genomic and epigenomic contexts. In this study, we compared genome-wide maps of 6-4PP and CPD lesion abundances in primary cells and conducted comprehensive analyses to determine the genetic and epigenetic features associated with susceptibility. Overall, we found a high degree of similarity between 6-4PP and CPD formation, with an enrichment of both in heterochromatin regions. However, when examining the relative levels of the two UV lesions, we found that bivalent and Polycomb-repressed chromatin states were uniquely more susceptible to 6-4PPs. Interestingly, when comparing UV susceptibility and repair with melanoma mutation frequency in these regions, disparate patterns were observed in that susceptibility was not always inversely associated with repair and mutation frequency. Functional enrichment analysis hint at mechanisms of negative selection for these regions that are essential for cell viability, immune function and induce cell death when mutated. Ultimately, these results reveal both the similarities and differences between UV-induced lesions that contribute to melanoma.</div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"823 ","pages":"Article 111758"},"PeriodicalIF":2.3,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mrfmmm.2021.111758","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39263477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Intronic variants of MITF (rs7623610) and CREB1 (rs10932201) genes may enhance splicing efficiency in human melanoma cell line MITF (rs7623610)和CREB1 (rs10932201)基因的内含子变异可能提高人类黑色素瘤细胞系的剪接效率

IF 2.3 4区医学

Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis Pub Date : 2021-07-01 DOI: 10.1016/j.mrfmmm.2021.111763

Juliana Carron , Caroline Torricelli , Janet Keller Silva , Lilian de Oliveira Coser , Carmen Silvia Passos Lima , Gustavo Jacob Lourenço

{"title":"Intronic variants of MITF (rs7623610) and CREB1 (rs10932201) genes may enhance splicing efficiency in human melanoma cell line","authors":"Juliana Carron , Caroline Torricelli , Janet Keller Silva , Lilian de Oliveira Coser , Carmen Silvia Passos Lima , Gustavo Jacob Lourenço","doi":"10.1016/j.mrfmmm.2021.111763","DOIUrl":"10.1016/j.mrfmmm.2021.111763","url":null,"abstract":"<div>We previously reported that intronic single nucleotide variations (SNVs) in MITF (c.938−325G>A, rs7623610) and CREB1 (c.303+373G>A, rs10932201) genes were associated with risk, aggressiveness, and prognosis of cutaneous melanoma (CM). In this study, we investigated the influence of the above SNVs in splicing patterns and efficiency. We constructed minigenes with wild type and variant alleles from MITF and CREB1 to assess the effect of the SNVs on splicing. The minigenes were transfected in the human melanoma cell line (SK-MEL-28). RT-PCR and DNA sequencing investigated the constructs’ splicing patterns. Minigenes constructs’ splicing efficiency and HNRNPA1 and SF1 splicing genes’ expression were investigated by qPCR. We found that MITF and CREB1 SNVs did not alter the splicing pattern, but they influenced the splicing efficiency. MITF-A (p= 0.03) and CREB1-A (p= 0.005) variant minigenes yielded an increase of mRNA generated from the constructions. Additionally, lower mRNA levels of HNRNPA1 and SF1 were seen in the variant minigenes MITF-A (p= 0.04) and CREB1-A (p= 0.005). We described for the first time the potential importance of MITF rs7623610 and CREB1 rs10932201 SNVs in splicing efficiency and its relationship with CM.</div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"823 ","pages":"Article 111763"},"PeriodicalIF":2.3,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39570741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mutational property of newly identified mutagen l-glutamic acid γ-hydrazide in Escherichia coli 新发现的诱变剂l-谷氨酸γ-肼在大肠杆菌中的突变特性

IF 2.3 4区医学

Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis Pub Date : 2021-07-01 DOI: 10.1016/j.mrfmmm.2021.111759

Tomoya Maeda , Atsushi Shibai , Naomi Yokoi , Yumeko Tarusawa , Masako Kawada , Hazuki Kotani , Chikara Furusawa

{"title":"Mutational property of newly identified mutagen l-glutamic acid γ-hydrazide in Escherichia coli","authors":"Tomoya Maeda , Atsushi Shibai , Naomi Yokoi , Yumeko Tarusawa , Masako Kawada , Hazuki Kotani , Chikara Furusawa","doi":"10.1016/j.mrfmmm.2021.111759","DOIUrl":"10.1016/j.mrfmmm.2021.111759","url":null,"abstract":"<div>We previously found that an l-glutamine analog l-glutamic acid γ-hydrazide has high mutagenic activity through the high-throughput laboratory evolution of Escherichia coli. In this study, mutagenicity and mutational property of l-glutamic acid γ-hydrazide were examined by the Ames test and mutation accumulation experiments using E. coli. The Ames test revealed that l-glutamic acid γ-hydrazide showed higher mutagenic activity without metabolic activation than known mutagens 2-aminoanthracene, and cobalt(II) acetate tetrahydrate. This result indicates that l-glutamic acid γ-hydrazide does not require metabolic activation for mutagenic activity in E. coli. Mutation accumulation experiments and whole-genome sequencing analysis revealed the number and spectrum of the accumulated mutations with or without l-glutamic acid γ-hydrazide. In the presence of l-glutamic acid γ-hydrazide, MDS42 strain accumulated 392.3 ± 116.2 point mutations during 30 passages corresponding to 777 generations, while MDS42 strain accumulated 1.5 ± 2.5 point mutations without l-glutamic acid γ-hydrazide during 50 passages corresponding to 1341 generations. The mutational spectrum of l-glutamic acid γ-hydrazide was G/C to A/T transition (82.2 ± 4.3 %) and A/T to G/C transition (17.4 ± 4.3 %). These results indicated that l-glutamic acid γ-hydrazide has a strong mutagenic activity.</div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"823 ","pages":"Article 111759"},"PeriodicalIF":2.3,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mrfmmm.2021.111759","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39219264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2