Pub Date : 2019-04-03eCollection Date: 2018-01-01DOI: 10.3934/genet.2018.4.192
Mi Young Son, Paul Hasty
Homologous recombination (HR) repairs DNA double strand breaks (DSBs) and stabilizes replication forks (RFs). RAD51 is the recombinase for the HR pathway. To preserve genomic integrity, RAD51 forms a filament on the 3' end of a DSB and on a single-stranded DNA (ssDNA) gap. But unregulated HR results in undesirable chromosomal rearrangements. This review describes the multiple mechanisms that regulate HR with a focus on those mechanisms that promote and contain RAD51 filaments to limit chromosomal rearrangements. If any of these pathways break down and HR becomes unregulated then disease, primarily cancer, can result.
{"title":"Homologous recombination defects and how they affect replication fork maintenance.","authors":"Mi Young Son, Paul Hasty","doi":"10.3934/genet.2018.4.192","DOIUrl":"10.3934/genet.2018.4.192","url":null,"abstract":"<p><p>Homologous recombination (HR) repairs DNA double strand breaks (DSBs) and stabilizes replication forks (RFs). RAD51 is the recombinase for the HR pathway. To preserve genomic integrity, RAD51 forms a filament on the 3' end of a DSB and on a single-stranded DNA (ssDNA) gap. But unregulated HR results in undesirable chromosomal rearrangements. This review describes the multiple mechanisms that regulate HR with a focus on those mechanisms that promote and contain RAD51 filaments to limit chromosomal rearrangements. If any of these pathways break down and HR becomes unregulated then disease, primarily cancer, can result.</p>","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6690234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47035043","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}
Abstract Intra-category hybrids of Carthamus tinctorius were analyzed for the genetic toxicity in detail for effect of Cd2+ + Cr6+ on reproductive biology of Carthamus tinctorius. Five partially tolerant and five non-tolerant accessions of Carthamus tinctorius after screening were crossed to produce intra-category hybrid. These two heavy metals in combination influenced antagonistically first as well as second meiotic divisions inducing various kinds of anomalies and reduced the number of pollen grains per anther and significantly increased pollen sterility. A differential response for the amount of meiotic irregularity was recorded between different treated sets of hybrids in (Cd + Cr) treated sets. This could be due to differential response of the genotypes for the same concentration of (Cd + Cr). These two heavy metals in combination reduced the number of pollen grains per anther and significantly increased pollen sterility.
{"title":"Cd2+ + Cr6+ causes toxic effects on chromosomal development of microspore in Carthamus tinctorius","authors":"N. Mittal, A. Srivastava","doi":"10.3934/genet.2019.1.1","DOIUrl":"https://doi.org/10.3934/genet.2019.1.1","url":null,"abstract":"Abstract Intra-category hybrids of Carthamus tinctorius were analyzed for the genetic toxicity in detail for effect of Cd2+ + Cr6+ on reproductive biology of Carthamus tinctorius. Five partially tolerant and five non-tolerant accessions of Carthamus tinctorius after screening were crossed to produce intra-category hybrid. These two heavy metals in combination influenced antagonistically first as well as second meiotic divisions inducing various kinds of anomalies and reduced the number of pollen grains per anther and significantly increased pollen sterility. A differential response for the amount of meiotic irregularity was recorded between different treated sets of hybrids in (Cd + Cr) treated sets. This could be due to differential response of the genotypes for the same concentration of (Cd + Cr). These two heavy metals in combination reduced the number of pollen grains per anther and significantly increased pollen sterility.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45508414","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}
Pub Date : 2018-12-01DOI: 10.3934/genet.2018.4.212
X. Xia
Abstract I analyzed various site pattern combinations in a 4-OTU case to identify sources of starless bias and parameter-estimation bias in likelihood-based phylogenetic methods, and reported three significant contributions. First, the likelihood method is counterintuitive in that it may not generate a star tree with sequences that are equidistant from each other. This behaviour, dubbed starless bias, happens in a 4-OTU tree when there is an excess (i.e., more than expected from a star tree and a substitution model) of conflicting phylogenetic signals supporting the three resolved topologies equally. Special site pattern combinations leading to rejection of a star tree, when sequences are equidistant from each other, were identified. Second, fitting gamma distribution to model rate heterogeneity over sites is strongly confounded with tree topology, especially in conjunction with the starless bias. I present examples to show dramatic differences in the estimated shape parameter Α between a star tree and a resolved tree. There may be no rate heterogeneity over sites (with the estimated Α > 10000) when a star tree is imposed, but Α < 1 (suggesting strong rate heterogeneity over sites) when an (incorrect) resolved tree is imposed. Thus, the dependence of “rate heterogeneity” on tree topology implies that “rate heterogeneity” is not a sequence-specific feature, cautioning against interpreting a small Α to mean that some sites are under strong purifying selection and others not. Thirdly, because there is no existing (and working) likelihood method for evaluating a star tree with continuous gamma-distributed rate, I have implemented the method for JC69 in a self-contained R script for a four-OTU tree (star or resolved), in addition to another R script assuming a constant rate over sites. These R scripts should be useful for teaching and exploring likelihood methods in phylogenetics.
{"title":"Starless bias and parameter-estimation bias in the likelihood-based phylogenetic method","authors":"X. Xia","doi":"10.3934/genet.2018.4.212","DOIUrl":"https://doi.org/10.3934/genet.2018.4.212","url":null,"abstract":"Abstract I analyzed various site pattern combinations in a 4-OTU case to identify sources of starless bias and parameter-estimation bias in likelihood-based phylogenetic methods, and reported three significant contributions. First, the likelihood method is counterintuitive in that it may not generate a star tree with sequences that are equidistant from each other. This behaviour, dubbed starless bias, happens in a 4-OTU tree when there is an excess (i.e., more than expected from a star tree and a substitution model) of conflicting phylogenetic signals supporting the three resolved topologies equally. Special site pattern combinations leading to rejection of a star tree, when sequences are equidistant from each other, were identified. Second, fitting gamma distribution to model rate heterogeneity over sites is strongly confounded with tree topology, especially in conjunction with the starless bias. I present examples to show dramatic differences in the estimated shape parameter Α between a star tree and a resolved tree. There may be no rate heterogeneity over sites (with the estimated Α > 10000) when a star tree is imposed, but Α < 1 (suggesting strong rate heterogeneity over sites) when an (incorrect) resolved tree is imposed. Thus, the dependence of “rate heterogeneity” on tree topology implies that “rate heterogeneity” is not a sequence-specific feature, cautioning against interpreting a small Α to mean that some sites are under strong purifying selection and others not. Thirdly, because there is no existing (and working) likelihood method for evaluating a star tree with continuous gamma-distributed rate, I have implemented the method for JC69 in a self-contained R script for a four-OTU tree (star or resolved), in addition to another R script assuming a constant rate over sites. These R scripts should be useful for teaching and exploring likelihood methods in phylogenetics.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44735194","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}
Pub Date : 2018-07-02DOI: 10.3934/genet.2018.3.177
Eun Jeong Kim, Yong-Ku Kim
Abstract Panic disorder is characterized by symptoms with abrupt surges of fear with palpitations, sweating, trembling, heat sensations. Considering its disease burden on each individual and on society, understanding its etiology is important. Though no one specific etiology has been known, like other psychiatric disorders, multiple factors such as genetic, environmental, neurobiological, psychopathological factors have been suggested. In this article, we reviewed currently known etiologies and related study results, regarding especially genetic and epigenetic aspects of the panic disorder. Early studies, including twin studies, family studies, adoption studies suggested highly familial trait of panic disorder. Linkage studies, either, found panic disorder is not a single gene disorder but confirmed existence of multiple related genes. Chromosome and candidate gene studies found few related genes, NPY, ADORA2A, COMT, IKBKE. Newer method, genome-wide association studies (GWAS) have been searching for newer genes. No genome-wide significant genes, however, were detected, confirming previously known candidate genes, NPY5R on 4q31.3-32, BDKRB2 on 14q32, instead. Epigenetic modification has also been studied on many different psychiatric disorders. Monoamine oxidase A (MAOA) hypomethylation, taken together with negative life events, showed relation with panic disorder. Glutamate decarbodylases 1 (GAD1) hypomethylation was also specific on panic disorder patients. Relation with noradrenaline transporter (NET) gene SLC6a2 promoter methylation has also been studied. In conclusion, no specific gene or epigenetic pattern can fully explain etiology of panic disorder. Few genes and epigenetic patterns, however, showed strong association with panic disorder compared to healthy controls. Considering its multivariable background, further studies with larger populations can confirm current results and clarify etiologies of panic disorder.
{"title":"Panic disorders: The role of genetics and epigenetics","authors":"Eun Jeong Kim, Yong-Ku Kim","doi":"10.3934/genet.2018.3.177","DOIUrl":"https://doi.org/10.3934/genet.2018.3.177","url":null,"abstract":"Abstract Panic disorder is characterized by symptoms with abrupt surges of fear with palpitations, sweating, trembling, heat sensations. Considering its disease burden on each individual and on society, understanding its etiology is important. Though no one specific etiology has been known, like other psychiatric disorders, multiple factors such as genetic, environmental, neurobiological, psychopathological factors have been suggested. In this article, we reviewed currently known etiologies and related study results, regarding especially genetic and epigenetic aspects of the panic disorder. Early studies, including twin studies, family studies, adoption studies suggested highly familial trait of panic disorder. Linkage studies, either, found panic disorder is not a single gene disorder but confirmed existence of multiple related genes. Chromosome and candidate gene studies found few related genes, NPY, ADORA2A, COMT, IKBKE. Newer method, genome-wide association studies (GWAS) have been searching for newer genes. No genome-wide significant genes, however, were detected, confirming previously known candidate genes, NPY5R on 4q31.3-32, BDKRB2 on 14q32, instead. Epigenetic modification has also been studied on many different psychiatric disorders. Monoamine oxidase A (MAOA) hypomethylation, taken together with negative life events, showed relation with panic disorder. Glutamate decarbodylases 1 (GAD1) hypomethylation was also specific on panic disorder patients. Relation with noradrenaline transporter (NET) gene SLC6a2 promoter methylation has also been studied. In conclusion, no specific gene or epigenetic pattern can fully explain etiology of panic disorder. Few genes and epigenetic patterns, however, showed strong association with panic disorder compared to healthy controls. Considering its multivariable background, further studies with larger populations can confirm current results and clarify etiologies of panic disorder.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41530478","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}
Pub Date : 2018-03-26eCollection Date: 2018-01-01DOI: 10.3934/genet.2018.2.124
Carlos García-Padilla, Amelia Aránega, Diego Franco
Cells display a set of RNA molecules at one time point, reflecting thus the cellular transcriptional steady state, configuring therefore its transcriptome. It is basically composed of two different classes of RNA molecules; protein-coding RNAs (cRNAs) and protein non-coding RNAs (ncRNAs). Sequencing of the human genome and subsequently the ENCODE project identified that more than 80% of the genome is transcribed in some type of RNA. Importantly, only 3% of these transcripts correspond to protein-coding RNAs, pointing that ncRNAs are as important or even more as cRNAs. ncRNAs have pivotal roles in development, differentiation and disease. Non-coding RNAs can be classified into two distinct classes according to their length; i.e., small (<200 nt) and long (>200 nt) noncoding RNAs. The structure, biogenesis and functional roles of small non-coding RNA have been widely studied, particularly for microRNAs (miRNAs). In contrast to microRNAs, our current understanding of long non-coding RNAs (lncRNAs) is limited. In this manuscript, we provide state-of-the art review of the functional roles of long non-coding RNAs during cardiac development as well as an overview of the emerging role of these ncRNAs in distinct cardiac diseases.
{"title":"The role of long non-coding RNAs in cardiac development and disease.","authors":"Carlos García-Padilla, Amelia Aránega, Diego Franco","doi":"10.3934/genet.2018.2.124","DOIUrl":"https://doi.org/10.3934/genet.2018.2.124","url":null,"abstract":"<p><p>Cells display a set of RNA molecules at one time point, reflecting thus the cellular transcriptional steady state, configuring therefore its transcriptome. It is basically composed of two different classes of RNA molecules; protein-coding RNAs (cRNAs) and protein non-coding RNAs (ncRNAs). Sequencing of the human genome and subsequently the ENCODE project identified that more than 80% of the genome is transcribed in some type of RNA. Importantly, only 3% of these transcripts correspond to protein-coding RNAs, pointing that ncRNAs are as important or even more as cRNAs. ncRNAs have pivotal roles in development, differentiation and disease. Non-coding RNAs can be classified into two distinct classes according to their length; i.e., small (<200 nt) and long (>200 nt) noncoding RNAs. The structure, biogenesis and functional roles of small non-coding RNA have been widely studied, particularly for microRNAs (miRNAs). In contrast to microRNAs, our current understanding of long non-coding RNAs (lncRNAs) is limited. In this manuscript, we provide state-of-the art review of the functional roles of long non-coding RNAs during cardiac development as well as an overview of the emerging role of these ncRNAs in distinct cardiac diseases.</p>","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41215474","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}
Pub Date : 2018-03-21eCollection Date: 2018-01-01DOI: 10.3934/genet.2018.2.113
Vadim Chagin, Andrei Zalensky, Igor Nazarov, Olga Mudrak
Chromosome positioning in sperm nucleus may have a functional significance by influencing the sequence of post-fertilization events. In this study we present data on preferential locations of chromosomes 1, 29 and X in Bos taurus spermatozoa. Here we demonstrate that the position of X chromosome in the sperm nucleus is more restricted as compared to the position of chromosome 1, which is about of the same size. Our data support the concept of the functional significance of genome architecture in male germline cells.
{"title":"Preferable location of chromosomes 1, 29, and X in bovine spermatozoa.","authors":"Vadim Chagin, Andrei Zalensky, Igor Nazarov, Olga Mudrak","doi":"10.3934/genet.2018.2.113","DOIUrl":"10.3934/genet.2018.2.113","url":null,"abstract":"<p><p>Chromosome positioning in sperm nucleus may have a functional significance by influencing the sequence of post-fertilization events. In this study we present data on preferential locations of chromosomes 1, 29 and X in <i>Bos taurus</i> spermatozoa. Here we demonstrate that the position of X chromosome in the sperm nucleus is more restricted as compared to the position of chromosome 1, which is about of the same size. Our data support the concept of the functional significance of genome architecture in male germline cells.</p>","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45061205","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}
Pub Date : 2018-03-19eCollection Date: 2018-01-01DOI: 10.3934/genet.2018.2.91
Valeriia Mikhailova, Valeriia Gulaia, Vladlena Tiasto, Stanislav Rybtsov, Margarita Yatsunskaya, Alexander Kagansky
The modulation of tumor growth and development in vitro has always been one of the key factors in the research of the malignant transformation, including gliomas, prevalent and most deadly cancers of the brain. Indeed, cellular and molecular biology research employing in vitro model cell-based systems have great potential to advance both the mechanistic understanding and the treatment of human glial tumors, as it facilitates not only the understanding of glioma biology and its regulatory mechanisms Additionally they promise to afford the screening of the putative anti-tumor agents and alternative treatment approaches in a personalized manner, i.e. by virtue of using the patient-derived tumor material for such tests. However, in order to become reliable and representative, glioma model systems need to move towards including most inherent cancer features such as local hypoxia, specific genetic aberrations, native tumor microenvironment, and the three-dimensional extracellular matrix. This review starts with a brief introduction on the general epidemiological and molecular characteristics of gliomas followed by an overview of the cell-based in vitro models currently used in glioma research. As a conclusion, we suggest approaches to move to innovative cell-based in vitro glioma models. We consider that main criteria for selecting these approaches should include the adequate resemblance to the key in vivo characteristics, robustness, cost-effectiveness and ease to use, as well as the amenability to high throughput handling to allow the standardized drug screening.
{"title":"Towards an advanced cell-based <i>in vitro</i> glioma model system.","authors":"Valeriia Mikhailova, Valeriia Gulaia, Vladlena Tiasto, Stanislav Rybtsov, Margarita Yatsunskaya, Alexander Kagansky","doi":"10.3934/genet.2018.2.91","DOIUrl":"https://doi.org/10.3934/genet.2018.2.91","url":null,"abstract":"<p><p>The modulation of tumor growth and development <i>in vitro</i> has always been one of the key factors in the research of the malignant transformation, including gliomas, prevalent and most deadly cancers of the brain. Indeed, cellular and molecular biology research employing <i>in vitro</i> model cell-based systems have great potential to advance both the mechanistic understanding and the treatment of human glial tumors, as it facilitates not only the understanding of glioma biology and its regulatory mechanisms Additionally they promise to afford the screening of the putative anti-tumor agents and alternative treatment approaches in a personalized manner, i.e. by virtue of using the patient-derived tumor material for such tests. However, in order to become reliable and representative, glioma model systems need to move towards including most inherent cancer features such as local hypoxia, specific genetic aberrations, native tumor microenvironment, and the three-dimensional extracellular matrix. This review starts with a brief introduction on the general epidemiological and molecular characteristics of gliomas followed by an overview of the cell-based <i>in vitro</i> models currently used in glioma research. As a conclusion, we suggest approaches to move to innovative cell-based <i>in vitro</i> glioma models. We consider that main criteria for selecting these approaches should include the adequate resemblance to the key <i>in vivo</i> characteristics, robustness, cost-effectiveness and ease to use, as well as the amenability to high throughput handling to allow the standardized drug screening.</p>","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41215475","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}
Pub Date : 2018-03-18DOI: 10.3934/genet.2018.2.161
H. Phung, H. Nguyen, D. Nguyen
Abstract Saccharomyces cerevisiae Mus81 is a structure-selective endonuclease which constitutes an alternative pathway in parallel with the helicase-topoisomerase Sgs1-Top3-Rmi1 complex to resolve a number of DNA intermediates during DNA replication, repair, and homologous recombination. Previously, it was showed that the N-terminal region of Mus81 was required for its in vivo function in a redundant manner with Sgs1; mus81Δ120N mutant that lacks the first 120 amino acid residues at the N-terminus exhibited synthetic lethality in combination with the loss of SGS1. In this study, the physiologically important role of the N-terminal region of Mus81 in processing toxic intermediates was further investigated. We examined the cellular defect of sgs1Δmus81Δ100N cells and observed that although viable, the cells became very sensitive to DNA damaging agents. A single-copy suppressor screening to seek for a factor(s) that could rescue the drug sensitivity of sgs1Δmus81Δ100N cells was performed and revealed that Flp1, a site-specific recombinase 1 encoded on the 2-micron plasmid was a suppressor. Moreover, Flp1 overexpression could partially suppress the drug sensitivity of mus81Δ cells at 37 °C. Our findings suggest a possible function of Flp1 in coordination with Mus81 and Sgs1 to jointly resolve the branched-DNA structures generated in cells attempting to repair DNA damages.
{"title":"The possible function of Flp1 in homologous recombination repair in Saccharomyces cerevisiae","authors":"H. Phung, H. Nguyen, D. Nguyen","doi":"10.3934/genet.2018.2.161","DOIUrl":"https://doi.org/10.3934/genet.2018.2.161","url":null,"abstract":"Abstract Saccharomyces cerevisiae Mus81 is a structure-selective endonuclease which constitutes an alternative pathway in parallel with the helicase-topoisomerase Sgs1-Top3-Rmi1 complex to resolve a number of DNA intermediates during DNA replication, repair, and homologous recombination. Previously, it was showed that the N-terminal region of Mus81 was required for its in vivo function in a redundant manner with Sgs1; mus81Δ120N mutant that lacks the first 120 amino acid residues at the N-terminus exhibited synthetic lethality in combination with the loss of SGS1. In this study, the physiologically important role of the N-terminal region of Mus81 in processing toxic intermediates was further investigated. We examined the cellular defect of sgs1Δmus81Δ100N cells and observed that although viable, the cells became very sensitive to DNA damaging agents. A single-copy suppressor screening to seek for a factor(s) that could rescue the drug sensitivity of sgs1Δmus81Δ100N cells was performed and revealed that Flp1, a site-specific recombinase 1 encoded on the 2-micron plasmid was a suppressor. Moreover, Flp1 overexpression could partially suppress the drug sensitivity of mus81Δ cells at 37 °C. Our findings suggest a possible function of Flp1 in coordination with Mus81 and Sgs1 to jointly resolve the branched-DNA structures generated in cells attempting to repair DNA damages.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47392969","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}
Pub Date : 2018-03-15DOI: 10.3934/genet.2018.2.141
Yekaterina Zvorykina, A. Tvorogova, A. Gladkikh, I. Vorobjev
Abstract Microtubules in interphase fibroblast-like cells are thought to be organized in a radial array growing from a centrosome-based microtubule-organizing center (MTOC) to the cell edges. However, many morphogenetic processes require the asymmetry of the microtubules (MT) array. One of the possible mechanisms of this asymmetry could be the presence of non-centrosomal microtubules in different intracellular areas. To evaluate the role of centrosome-born and non-centrosomal microtubules in the organization of microtubule array in motile 3T3 fibroblasts, we have performed the high-throughput analysis of microtubule growth in different functional zones of the cell and distinguished three subpopulations of growing microtubules (centrosome-born, marginal and inner cytoplasmic). Centrosome as an active microtubule-organizing center was absent in half of the cell population. However, these cells do not show any difference in microtubule growth pattern. In cells with active centrosome, it was constantly forming short (ephemeral) MTs, and ∼15–20 MT per minute grow outwards for a distance >1 µm. Almost no persistent growth of microtubules was observed in these cells with the average growth length of 5–6 µm and duration of growth periods within 30 s. However, the number of growing ends increased towards cell margin, especially towards the active edges. We found the peripheral cytoplasmic foci of microtubule growth there. During recovery from nocodazole treatment microtubules started to grow around the centrosome in a normal way and independently in all the cell areas. Within 5 minutes microtubules continued to grow mainly near the cell edge. Thus, our data confirm the negligible role of centrosome as MTOC in 3T3 fibroblasts and propose a model of non-centrosomal microtubules as major players that create the cell asymmetry in the cells with a mesenchymal type of motility. We suggest that increased density of dynamic microtubules near the active lamellum could be supported by microtubule-based microtubule nucleation.
{"title":"Non-centrosomal MTs play a crucial role in organization of MT array in interphase fibroblasts","authors":"Yekaterina Zvorykina, A. Tvorogova, A. Gladkikh, I. Vorobjev","doi":"10.3934/genet.2018.2.141","DOIUrl":"https://doi.org/10.3934/genet.2018.2.141","url":null,"abstract":"Abstract Microtubules in interphase fibroblast-like cells are thought to be organized in a radial array growing from a centrosome-based microtubule-organizing center (MTOC) to the cell edges. However, many morphogenetic processes require the asymmetry of the microtubules (MT) array. One of the possible mechanisms of this asymmetry could be the presence of non-centrosomal microtubules in different intracellular areas. To evaluate the role of centrosome-born and non-centrosomal microtubules in the organization of microtubule array in motile 3T3 fibroblasts, we have performed the high-throughput analysis of microtubule growth in different functional zones of the cell and distinguished three subpopulations of growing microtubules (centrosome-born, marginal and inner cytoplasmic). Centrosome as an active microtubule-organizing center was absent in half of the cell population. However, these cells do not show any difference in microtubule growth pattern. In cells with active centrosome, it was constantly forming short (ephemeral) MTs, and ∼15–20 MT per minute grow outwards for a distance >1 µm. Almost no persistent growth of microtubules was observed in these cells with the average growth length of 5–6 µm and duration of growth periods within 30 s. However, the number of growing ends increased towards cell margin, especially towards the active edges. We found the peripheral cytoplasmic foci of microtubule growth there. During recovery from nocodazole treatment microtubules started to grow around the centrosome in a normal way and independently in all the cell areas. Within 5 minutes microtubules continued to grow mainly near the cell edge. Thus, our data confirm the negligible role of centrosome as MTOC in 3T3 fibroblasts and propose a model of non-centrosomal microtubules as major players that create the cell asymmetry in the cells with a mesenchymal type of motility. We suggest that increased density of dynamic microtubules near the active lamellum could be supported by microtubule-based microtubule nucleation.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41905053","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}