Mutation Research/DNA Repair最新文献

{"title":"The two-step model for translesion synthesis: then and now","authors":"Bryn Bridges","doi":"10.1016/S0921-8777(00)00074-4","DOIUrl":"10.1016/S0921-8777(00)00074-4","url":null,"abstract":"<div><p><span><span>The formation of base substitution mutations following exposure of bacteria to ultraviolet light and many other </span>mutagens occurs during translesion synthesis opposite a photoproduct or other lesion in the template strand of DNA. This process requires the UmuD</span>₂′ UmuC complex, only formed to a significant extent in SOS-induced cells. The “two-step” model proposed that there were two steps, insertion of a wrong base (misincorporation) and use of the misincorporated base as a primer for further chain extension (bypass). The original evidence suggested that UmuD₂′ UmuC was needed only for the second step and that in its absence other polymerases such as DNA polymerase III could make misincorporations. Now we know that the UmuD₂<span>′ UmuC complex is DNA polymerase V<span><span> and that it can carry out both steps in vitro and probably does both in vivo in wild-type cells. Even so, DNA polymerase III clearly has an important accessory role in vitro and a possibly essential role in vivo, the precise nature of which is not clear. DNA polymerases II and IV are also up-regulated in SOS-induced cells and their involvement in the broader picture of translesion synthesis is only now beginning to emerge. It is suggested that we need to think of the </span>chromosomal replication factory as a structure through which the DNA passes and within which as many as five DNA polymerases may need to act. Protein–protein interactions may result in a cassette system in which the most appropriate polymerase can be engaged with the DNA at any given time. The original two-step model was very specific, and thus an oversimplification. As a general concept, however, it reflects reality and has been demonstrated in experiments with eukaryotic DNA polymerases in vitro.</span></span></p></div>","PeriodicalId":100935,"journal":{"name":"Mutation Research/DNA Repair","volume":"485 1","pages":"Pages 61-67"},"PeriodicalIF":0.0,"publicationDate":"2001-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0921-8777(00)00074-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56179600","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}

{"title":"From xeroderma pigmentosum to the biological clock contributions of Dirk Bootsma to human genetics","authors":"Jan H.J. Hoeijmakers","doi":"10.1016/S0921-8777(00)00079-3","DOIUrl":"10.1016/S0921-8777(00)00079-3","url":null,"abstract":"<div><p><span><span><span>This paper commemorates the multiple contributions of Dirk Bootsma to human genetics. During a scientific ‘Bootsma’ cruise on his sailing-boat ‘de Losbol’, we visit a variety of scenery locations along the lakes and canals in Friesland, passing the highlights of Dirk Bootsma’s scientific oeuvre. Departing from ‘de Fluessen’, his homeport, with his PhD work on the effect of X-rays and UV on cell cycle progression, we head for the pioneering endeavours of his team on mapping genes on </span>human chromosomes<span> by cell hybridization. Next we explore the use of cell hybrids by the Bootsma team culminating in the </span></span>molecular cloning of one of the first chromosomal breakpoints involved in oncogenesis: the </span><em>bcr-abl</em><span><span><span> fusion gene responsible for chronic myelocytic leukemia. This seminal achievement enabled later development of new methods for early detection and very promising therapeutic intervention. A series of highlights at the horizon constitute the contributions of his team to the field of DNA repair, beginning with the discovery of genetic heterogeneity<span> in the repair syndrome xeroderma pigmentosum (XP) followed later by the cloning of a large number of human repair genes. This led to the discovery that DNA repair is strongly conserved in evolution rendering knowledge from yeast relevant for mammals and vice versa. In addition, it resolved the molecular basis of several repair syndromes and permitted functional analysis of the encoded proteins. Another milestone is the discovery of the surprising connection between DNA repair and </span></span>transcription initiation<span> via the dual functional TFIIH complex in collaboration with Jean-Marc Egly et al. in Strasbourg. This provided an explanation for many puzzling clinical features and triggered a novel concept in human genetics: the existence of repair/transcription syndromes. The generation of many mouse mutants carrying defects in repair pathways yielded valuable models for assessing the clinical relevance of DNA repair including carcinogenesis and the identification of a link between DNA damage and premature aging. His team also opened a fascinating area of cell biology with the analysis of repair and transcription in living cells. A final surprising evolutionary twist was the discovery that </span></span>photolyases<span> designed for the light-dependent repair of UV-induced DNA lesions appeared to be adopted for driving the mammalian biological clock<span>. The latter indicates that it is time to return to ‘de Fluessen’, where we will consider briefly the merits of Dirk Bootsma for Dutch science in general.</span></span></span></p></div>","PeriodicalId":100935,"journal":{"name":"Mutation Research/DNA Repair","volume":"485 1","pages":"Pages 43-59"},"PeriodicalIF":0.0,"publicationDate":"2001-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0921-8777(00)00079-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56179649","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}

{"title":"Gene and sequence specificity of DNA damage induction and repair: consequences for mutagenesis","authors":"Albert A. van Zeeland,&nbsp;Leon H.F. Mullenders,&nbsp;Harry Vrieling","doi":"10.1016/S0921-8777(00)00072-0","DOIUrl":"10.1016/S0921-8777(00)00072-0","url":null,"abstract":"<div><p><span><span>The field of DNA repair has been expanded enormously in the last 20 years. In this paper, work on gene and sequence specificity of DNA damage induction and repair is summarized in the light of the large and broad contribution of Phil Hanawalt to this field of research. Furthermore, the consequences of DNA damage and repair for mutation induction is discussed, and the contribution of Paul Lohman to the development of assays employing </span>transgenic mice for the detection of </span>gene mutations is highlighted.</p></div>","PeriodicalId":100935,"journal":{"name":"Mutation Research/DNA Repair","volume":"485 1","pages":"Pages 15-21"},"PeriodicalIF":0.0,"publicationDate":"2001-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0921-8777(00)00072-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56179580","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}

{"title":"Nucleotide excision repair “a legacy of creativity”","authors":"J.E. Cleaver ,&nbsp;K. Karplus ,&nbsp;M. Kashani-Sabet ,&nbsp;C.L. Limoli","doi":"10.1016/S0921-8777(00)00073-2","DOIUrl":"10.1016/S0921-8777(00)00073-2","url":null,"abstract":"<div><p><span>The first half of the 20th century has seen an enormous growth in our knowledge of DNA repair, in no small part due to the work of Dirk Bootsma, Philip Hanawalt and Bryn Bridges; those honored by this issue. For the new millennium, we have asked three general questions: (A) Do we know all possible strategies of nucleotide excision repair (NER) in all organisms? (B) How is NER integrated and regulated in cells and tissues? (C) Does DNA replication represent a new frontier in the roles of DNA repair? We make some suggestions for the kinds of answers the next generation may provide. The kingdom of archea represents an untapped field for investigation of DNA repair in organisms with extreme lifestyles. NER appears to involve a similar strategy to the other kingdoms of </span>prokaryotes<span><span> and eukaryotes, but subtle differences suggest that individual components of the system may differ. NER appears to be regulated by several major factors, especially p53 and Rb which interact with transcription coupled repair and global genomic repair, respectively. Examples can be found of major regulatory changes in repair in testicular tissue and melanoma cells. Our understanding of replication of damaged DNA has undergone a revolution in recent years, with the discovery of multiple low-fidelity DNA polymerases that facilitate replicative bypass. A secondary mechanism of replication in the absence of NER or of one or more of these polymerases involves </span>sister chromatid exchange and recombination (hMre11/hRad50/Nbs1). The relative importance of bypass and recombination is determined by the action of p53. We hypothesise that these polymerases may be involved in resolution of complex DNA structures during completion of replication and sister chromatid resolution. With these fascinating problems to investigate, the field of DNA repair will surely not disappoint the next generation.</span></p></div>","PeriodicalId":100935,"journal":{"name":"Mutation Research/DNA Repair","volume":"485 1","pages":"Pages 23-36"},"PeriodicalIF":0.0,"publicationDate":"2001-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0921-8777(00)00073-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56179590","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}

{"title":"Introduction to special issue on 40 years of DNA repair","authors":"Errol C. Friedberg,&nbsp;Kiyoji Tanaka,&nbsp;Albert A. van Zeeland (Special Issue Editors)","doi":"10.1016/S0921-8777(00)00070-7","DOIUrl":"https://doi.org/10.1016/S0921-8777(00)00070-7","url":null,"abstract":"","PeriodicalId":100935,"journal":{"name":"Mutation Research/DNA Repair","volume":"485 1","pages":"Page 1"},"PeriodicalIF":0.0,"publicationDate":"2001-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0921-8777(00)00070-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72064817","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}

{"title":"Bryn Bridges and mutagenesis: exploring the intellectual space","authors":"Graham C. Walker","doi":"10.1016/S0921-8777(00)00075-6","DOIUrl":"10.1016/S0921-8777(00)00075-6","url":null,"abstract":"<div><p>The products of the SOS-regulated <em>umuDC</em><span> genes are required for most UV and chemical mutagenesis in </span><em>Escherichia</em> <em>coli</em>. Recently it has been recognized that UmuC is the founding member of a superfamily of novel DNA polymerases found in all three kingdoms of life. Key findings leading to these insights are reviewed, placing a particular emphasis on contributions made by Bryn Bridges and on his interest in the importance of interactions between the <em>umuDC</em> gene products and the replicative DNA polymerase.</p></div>","PeriodicalId":100935,"journal":{"name":"Mutation Research/DNA Repair","volume":"485 1","pages":"Pages 69-81"},"PeriodicalIF":0.0,"publicationDate":"2001-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0921-8777(00)00075-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56179611","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}

{"title":"Evolution of the two-step model for UV-mutagenesis","authors":"Roger Woodgate","doi":"10.1016/S0921-8777(00)00076-8","DOIUrl":"10.1016/S0921-8777(00)00076-8","url":null,"abstract":"<div><p><span>It is quite remarkable how our understanding of translesion DNA synthesis (TLS) has changed so dramatically in the past 2 years. Until very recently, little was known about the molecular mechanisms of TLS in higher eukaryotes and what we did know, was largely based upon </span><em>Escherichia coli</em> and <span><em>Saccharomyces</em><em> cerevisiae</em></span> model systems. The paradigm, proposed by Bryn Bridges and I [Mutat. Res. 150 (1985) 133] in 1985, was that error-prone TLS occurred in two steps; namely a misinsertion event opposite a lesion, followed by extension of the mispair so as to facilitate complete bypass of the lesion. The initial concept was that at least for <em>E. coli</em><span>, the misinsertion event was performed by the cell’s main replicase, DNA polymerase III holoenzyme<span>, and that elongation was achieved through the actions of specialized polymerase accessory proteins, such as UmuD and UmuC. Some 15 years later, we now know that this view is likely to be incorrect in that both misinsertion </span></span><em>and</em> bypass are performed by the Umu proteins (now called pol V). As pol V is normally a distributive enzyme, pol III may only be required to “fix” the misincorporation as a mutation by completing chromosome duplication. However, while the role of the <em>E. coli</em> proteins involved in TLS have changed, the initial concept of misincorporation followed by extension/bypass remains valid. Indeed, recent evidence suggests that it can equally be applied to TLS in eukaryotic cells where there are many more DNA polymerases to choose from. The aim of this review is, therefore, to provide a historical perspective to the “two-step” model for UV-mutagenesis, how it has recently evolved, and in particular, to highlight the seminal contributions made to it by Bryn Bridges.</p></div>","PeriodicalId":100935,"journal":{"name":"Mutation Research/DNA Repair","volume":"485 1","pages":"Pages 83-92"},"PeriodicalIF":0.0,"publicationDate":"2001-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0921-8777(00)00076-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56179619","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}

{"title":"The “Dutch DNA Repair Group”, in retrospect","authors":"Dirk Bootsma","doi":"10.1016/S0921-8777(00)00080-X","DOIUrl":"10.1016/S0921-8777(00)00080-X","url":null,"abstract":"<div><p><span><span>The “Dutch DNA Repair Group” was established about 35 years ago. In this brief historical review some of the crucial decisions are described that have contributed to the relative success of the research of this group. The emphasis of the work of this group has been for many years on the genetic analysis of nucleotide excision repair (NER) and genetic diseases based on defects in this repair process: </span>xeroderma pigmentosum (XP), </span>Cockayne syndrome and trichothiodystrophy.</p></div>","PeriodicalId":100935,"journal":{"name":"Mutation Research/DNA Repair","volume":"485 1","pages":"Pages 37-41"},"PeriodicalIF":0.0,"publicationDate":"2001-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0921-8777(00)00080-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56179661","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}

{"title":"Induced mutagenic effects in the nucleotide excision repair deficient Drosophila mutant mus201D1, expressing a truncated XPG protein","authors":"Fabienne M.G.R. Calléja ,&nbsp;Madeleine J.M. Nivard ,&nbsp;Jan C.J. Eeken","doi":"10.1016/S0921-8777(00)00055-0","DOIUrl":"10.1016/S0921-8777(00)00055-0","url":null,"abstract":"<div><p><span><span>Defects in nucleotide excision repair (NER) as defined by the UV sensitivity of </span>xeroderma pigmentosum (XP), </span>Cockayne syndrome<span> (CS) and trichothiodystrophy (TTD) patients has lead to the identification of most of the genes involved: XPA through XPG, CSA and CSB. Whereas XP patients often show an increased risk for skin cancer after exposure to sunlight, this is not the case for patients with CS and TTD. Several CS patients have been shown to carry a defect in the XPG gene. The XPG, a structure specific endonuclease makes the incision 3′ of damage and is also involved in the subsequent 5′incision during the NER process. In addition, XPG plays a role in the removal of oxidative DNA damage.</span></p><p>The <em>Drosophila</em> XPG gene was isolated and based on the molecular defect of a spontaneous (insertion) and an EMS induced mutant, it was shown that a mutated XPG is responsible for the <em>Drosophila</em> mutagen-sensitive mutants <em>mus201</em>. One of these mutants, <em>mus201^D1</em> has been used extensively in studies of the effects and mechanisms of many chemical mutagens as well as X-rays. The results of these studies are discussed in the light of the finding that mus201p is the <em>Drosophila</em> homologue of XPG.</p></div>","PeriodicalId":100935,"journal":{"name":"Mutation Research/DNA Repair","volume":"461 4","pages":"Pages 279-288"},"PeriodicalIF":0.0,"publicationDate":"2001-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0921-8777(00)00055-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21929090","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}

{"title":"tert-Butoxyl radicals generate mainly 7,8-dihydro-8-oxoguanine in DNA","authors":"Hanns-Christian Mahler ,&nbsp;Ina Schulz ,&nbsp;Waldemar Adam ,&nbsp;Günther N Grimm ,&nbsp;Chantu R Saha-Möller ,&nbsp;Bernd Epe","doi":"10.1016/S0921-8777(00)00057-4","DOIUrl":"10.1016/S0921-8777(00)00057-4","url":null,"abstract":"<div><p><span>Like hydroxyl radicals, alkoxyl radicals have been implicated in the generation of cellular oxidative DNA damage under physiological conditions; however, their genotoxic potential has not yet been established. We have analyzed the DNA damage induced by a photochemical source of </span><em>tert-</em>butoxyl radicals, the water soluble peroxy ester [4-(<em>tert</em>-butyldioxycarbonyl)benzyl]triethylammonium chloride (BCBT), using various repair endonucleases as probes. The irradiation (UV³⁶⁰) of BCBT in the presence of bacteriophage PM2 DNA was found to generate a DNA damage profile that consisted mostly of base modifications sensitive to the repair endonuclease Fpg protein. Approximately 90% of the modifications were identified as 7,8-dihydro-8-oxoguanine (8-oxoGua) residues by HPLC/ECD analysis. Oxidative pyrimidine modifications (sensitive to endonuclease III), sites of base loss (AP sites) and single-strand breaks were only minor modifications. Experiments with various scavengers and quenchers indicated that the DNA damage by BCBT+UV³⁶⁰ was caused by <em>tert-</em><span>butoxyl radicals as the ultimate reactive species. The mutagenicity associated with the induced damage was analyzed in the </span><span><em>gpt</em></span> gene of plasmid pSV2<em>gpt</em>, which was exposed to BCBT+UV³⁶⁰ and subsequently transfected into <em>Escherichia coli</em><span><span>. The results were in agreement with the specific generation of 8-oxoGua. Nearly all point mutations (20 out of 21) were found to be GC→TA </span>transversions known to be characteristic for 8-oxoGua. In conclusion, alkoxyl radicals generated from BCBT+UV</span>³⁶⁰<span><span> induce 8-oxoGua in DNA with a higher selectivity than any other </span>reactive oxygen species analyzed so far.</span></p></div>","PeriodicalId":100935,"journal":{"name":"Mutation Research/DNA Repair","volume":"461 4","pages":"Pages 289-299"},"PeriodicalIF":0.0,"publicationDate":"2001-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0921-8777(00)00057-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21929091","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}