EnzymesPub Date : 2022-01-01Epub Date: 2022-11-07DOI: 10.1016/bs.enz.2022.10.001
Fuyuhiko Tamanoi, Kenichi Yoshikawa
{"title":"Summary of volume 51: DNA damage and double-strand breaks.","authors":"Fuyuhiko Tamanoi, Kenichi Yoshikawa","doi":"10.1016/bs.enz.2022.10.001","DOIUrl":"https://doi.org/10.1016/bs.enz.2022.10.001","url":null,"abstract":"<p><p>DNA damage and breaks are events that happen to DNA which exert a variety of influence on cell physiology including inhibition of DNA synthesis, repair response, cell cycle effect and cell death. Thus, it is important to deepened understanding of these events. In volume 51, we discussed topics including (1) assays to detect double-strand breaks, (2) conditions leading to double-strand breaks, (3) effects of irradiation, (4) DNA structure and chromatins, and (5) direct and indirect effect on DNA. Contributing authors and a table of contents for volume 51 are mentioned. We also discuss further issues and topics that need to be featured in future volumes. These include DNA damage sensors, DNA damage response proteins, and double-strand break repair pathways.</p>","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"52 ","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40722194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EnzymesPub Date : 2022-01-01Epub Date: 2022-09-27DOI: 10.1016/bs.enz.2022.08.005
Natsuko Kondo
{"title":"DNA damage and biological responses induced by Boron Neutron Capture Therapy (BNCT).","authors":"Natsuko Kondo","doi":"10.1016/bs.enz.2022.08.005","DOIUrl":"https://doi.org/10.1016/bs.enz.2022.08.005","url":null,"abstract":"<p><p>Boron Neutron Capture Therapy (BNCT) is a tumor cell selective high LET (linear energy transfer) particle beam therapy. The patient is administrated a boron (<sup>10</sup>B) compound via intravenous injection or infusion, and when <sup>10</sup>B is sufficiently accumulated in the tumor, neutron beams containing epithermal neutrons as the main component are irradiated. Epithermal neutrons lose energy in the body and become thermal neutrons. The captured <sup>10</sup>B undergoes a (n, α) reaction with thermal neutrons, and the resulting α particles and <sup>7</sup>Li nuclei have short ranges of 9-10μm and 4-5μm, respectively, and do not reach the surrounding cells in normal tissues. Therefore, these high LET-heavy charged particles can selectively kill cancer cells. The cell-killing effect of these heavy charged particles is thought to be triggered by DNA damage. It is known that DNA damage caused by heavy charged particles is more serious and difficult to repair than DNA damage caused by Low LET radiation such as X-rays and γ-rays. This review focuses on DNA damage, e.g., DNA strand breaks and DNA damage repair caused by BNCT and describes the resulting biological response.</p>","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"51 ","pages":"65-78"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40682358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EnzymesPub Date : 2022-01-01Epub Date: 2022-11-07DOI: 10.1016/bs.enz.2022.10.002
Fuyuhiko Tamanoi, Kenichi Yoshikawa
{"title":"Inhibition of DNA synthesis and cancer therapies.","authors":"Fuyuhiko Tamanoi, Kenichi Yoshikawa","doi":"10.1016/bs.enz.2022.10.002","DOIUrl":"https://doi.org/10.1016/bs.enz.2022.10.002","url":null,"abstract":"<p><p>Cancer is a worldwide problem afflicting 19 million people. Inhibition of DNA synthesis has been a cornerstone of anticancer therapy. A variety of chemotherapy drugs have been developed and many of these are aimed at inhibiting DNA synthesis, as they damage DNA, form DNA adduct and interfere with DNA synthesis. Another type of chemotherapy interferes with the synthesis of nucleotide pools. There are also other types of drugs that inhibit topoisomerases resulting in the interference with DNA replication and transcription. Significant progress has been made regarding radiation therapy that includes X-ray (and γ-ray), proton therapy and heavy ion therapy. The Auger therapy is a type of radiation therapy that differs from X-ray, proton or heavy ion therapy. The method relies on the use of high Z elements such as gadolinium, iodine, gold or silver. Irradiation of these elements results in the release of electrons including the Auger electrons that have strong DNA damaging effect. Tamanoi et al. developed novel nanoparticles containing gadolinium or iodine to place high Z elements at the periphery of the nucleus thus localizing them close to DNA. Irradiation with monochromatic X-ray resulted in the formation of double-strand DNA breaks leading to the destruction of tumor mass. Comparison of conventional X-ray therapy and the Auger therapy is discussed.</p>","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"52 ","pages":"11-21"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40722195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EnzymesPub Date : 2022-01-01Epub Date: 2022-11-09DOI: 10.1016/bs.enz.2022.10.005
Fuyuhiko Tamanoi
{"title":"The enzymes second edition part 2.","authors":"Fuyuhiko Tamanoi","doi":"10.1016/bs.enz.2022.10.005","DOIUrl":"https://doi.org/10.1016/bs.enz.2022.10.005","url":null,"abstract":"<p><p>Publication of the second edition of The Enzymes series was initiated in 1959 and eight volumes were published. This chapter describes volumes 4-8. All eight volumes were edited by Paul D. Boyer, Henry Lardy and Karl Myerback. Authors and chapter titles are listed.</p>","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"52 ","pages":"45-79"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40494149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EnzymesPub Date : 2021-01-01Epub Date: 2021-09-24DOI: 10.1016/bs.enz.2021.07.007
Tatiana V Ilina, Teresa Brosenitsch, Nicolas Sluis-Cremer, Rieko Ishima
{"title":"Retroviral RNase H: Structure, mechanism, and inhibition.","authors":"Tatiana V Ilina, Teresa Brosenitsch, Nicolas Sluis-Cremer, Rieko Ishima","doi":"10.1016/bs.enz.2021.07.007","DOIUrl":"https://doi.org/10.1016/bs.enz.2021.07.007","url":null,"abstract":"<p><p>All retroviruses encode the enzyme, reverse transcriptase (RT), which is involved in the conversion of the single-stranded viral RNA genome into double-stranded DNA. RT is a multifunctional enzyme and exhibits DNA polymerase and ribonuclease H (RNH) activities, both of which are essential to the reverse-transcription process. Despite the successful development of polymerase-targeting antiviral drugs over the last three decades, no bona fide inhibitor against the RNH activity of HIV-1 RT has progressed to clinical evaluation. In this review article, we describe the retroviral RNH function and inhibition, with primary consideration of the structural aspects of inhibition.</p>","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":" ","pages":"227-247"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8994160/pdf/nihms-1790289.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39958015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EnzymesPub Date : 2021-01-01Epub Date: 2021-09-01DOI: 10.1016/bs.enz.2021.07.006
Ekaterina Knyazhanskaya, Marc C Morais, Kyung H Choi
{"title":"Flavivirus enzymes and their inhibitors.","authors":"Ekaterina Knyazhanskaya, Marc C Morais, Kyung H Choi","doi":"10.1016/bs.enz.2021.07.006","DOIUrl":"https://doi.org/10.1016/bs.enz.2021.07.006","url":null,"abstract":"<p><p>Flaviviruses such as dengue, Japanese encephalitis, West Nile, Yellow Fever and Zika virus, cause viral hemorrhagic fever and encephalitis in humans. However, antiviral therapeutics to treat or prevent flavivirus infections are not yet available. Thus, there is pressing need to develop therapeutics and vaccines that target flavivirus infections. All flaviviruses carry a positive-sense single-stranded RNA genome, which encodes ten proteins; three structural proteins form the virus shell, and seven nonstructural (NS) proteins are involved in replication of the viral genome. While all NS proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) are part of a functional membrane-bound replication complex, enzymatic activities required for flaviviral replication reside in only two NS proteins, NS3 and NS5. NS3 functions as a protease, helicase, and triphosphatase, and NS5 as a capping enzyme, methyltransferase, and RNA-dependent RNA polymerase. In this chapter, we provide an overview of viral replication focusing on the structure and function of NS3 and NS5 replicases. We further describe strategies and examples of current efforts to identify potential flavivirus inhibitors against NS3 and NS5 enzymatic activities that can be developed as therapeutic agents to combat flavivirus infections.</p>","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":" ","pages":"265-303"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8717743/pdf/nihms-1765121.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39560060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EnzymesPub Date : 2021-01-01Epub Date: 2021-09-23DOI: 10.1016/bs.enz.2021.07.005
Emmanuelle Pitre, Aartjan J W Te Velthuis
{"title":"Understanding viral replication and transcription using single-molecule techniques.","authors":"Emmanuelle Pitre, Aartjan J W Te Velthuis","doi":"10.1016/bs.enz.2021.07.005","DOIUrl":"https://doi.org/10.1016/bs.enz.2021.07.005","url":null,"abstract":"<p><p>DNA and RNA viruses depend on one or more enzymes to copy and transcribe their genome, such as a polymerase, helicase, or exonuclease. Because of the important role of these enzymes in the virus replication cycle, they are key targets for antiviral development. To better understand the function of these enzymes and their interactions with host and viral factors, biochemical, structural and single-molecule approaches have been used to study them. Each of these techniques has its own strengths, and single-molecule methods have proved particularly powerful in providing insight into the step-sizes of motor proteins, heterogeneity of enzymatic activities, transient conformational changes, and force-sensitivity of reactions. Here we will discuss how single-molecule FRET, magnetic tweezers, optical tweezers, atomic force microscopy and flow stretching approaches have revealed novel insights into polymerase fidelity, the mechanism of action of antivirals, and the protein choreography within replication complexes.</p>","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":" ","pages":"83-113"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39560064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EnzymesPub Date : 2021-01-01DOI: 10.1016/S1874-6047(21)00035-4
Craig E Cameron, Jamie J Arnold, Laurie S Kaguni
{"title":"Preface.","authors":"Craig E Cameron, Jamie J Arnold, Laurie S Kaguni","doi":"10.1016/S1874-6047(21)00035-4","DOIUrl":"https://doi.org/10.1016/S1874-6047(21)00035-4","url":null,"abstract":"","PeriodicalId":39097,"journal":{"name":"Enzymes","volume":"49 ","pages":"xiii-xiv"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39560066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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