The Experts below are selected from a list of 312 Experts worldwide ranked by ideXlab platform
Makkuni Jayaram - One of the best experts on this subject based on the ideXlab platform.
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a flp sumo hybrid recombinase reveals multi layered copy number control of a Selfish DNA element through post translational modification
PLOS Genetics, 2019Co-Authors: Boyu Su, Anna Maciaszek, Piotr Guga, Makkuni JayaramAbstract:Mechanisms for highly efficient chromosome-associated equal segregation, and for maintenance of steady state copy number, are at the heart of the evolutionary success of the 2-micron plasmid as a stable multi-copy extra-chromosomal Selfish DNA element present in the yeast nucleus. The Flp site-specific recombination system housed by the plasmid, which is central to plasmid copy number maintenance, is regulated at multiple levels. Transcription of the FLP gene is fine-tuned by the repressor function of the plasmid-coded partitioning proteins Rep1 and Rep2 and their antagonist Raf1, which is also plasmid-coded. In addition, the Flp protein is regulated by the host’s post-translational modification machinery. Utilizing a Flp-SUMO fusion protein, which functionally mimics naturally sumoylated Flp, we demonstrate that the modification signals ubiquitination of Flp, followed by its proteasome-mediated degradation. Furthermore, reduced binding affinity and cooperativity of the modified Flp decrease its association with the plasmid FRT (Flp recombination target) sites, and/or increase its dissociation from them. The resulting attenuation of strand cleavage and recombination events safeguards against runaway increase in plasmid copy number, which is deleterious to the host—and indirectly—to the plasmid. These results have broader relevance to potential mechanisms by which Selfish genomes minimize fitness conflicts with host genomes by holding in check the extra genetic load they pose.
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hitchhiking on chromosomes a persistence strategy shared by diverse Selfish DNA elements
Plasmid, 2019Co-Authors: Santanu Ghosh, Makkuni JayaramAbstract:Abstract An underlying theme in the segregation of low-copy bacterial plasmids is the assembly of a ‘segrosome’ by DNA-protein and protein-protein interactions, followed by energy-driven directed movement. Analogous partitioning mechanisms drive the segregation of host chromosomes as well. Eukaryotic extra-chromosomal elements, exemplified by budding yeast plasmids and episomes of certain mammalian viruses, harbor partitioning systems that promote their physical association with chromosomes. In doing so, they indirectly take advantage of the spindle force that directs chromosome movement to opposite cell poles. Molecular-genetic, biochemical and cell biological studies have revealed several unsuspected aspects of ‘chromosome hitchhiking’ by the yeast 2-micron plasmid, including the ability of plasmid sisters to associate symmetrically with sister chromatids. As a result, the plasmid overcomes the ‘mother bias’ experienced by plasmids lacking a partitioning system, and elevates itself to near chromosome status in equal segregation. Chromosome association for stable propagation, without direct energy expenditure, may also be utilized by a small minority of bacterial plasmids–at least one case has been reported. Given the near perfect accuracy of chromosome segregation, it is not surprising that elements residing in evolutionarily distant host organisms have converged upon the common strategy of gaining passage to daughter cells as passengers on chromosomes.
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a Selfish DNA element engages a meiosis specific motor and telomeres for germ line propagation
Journal of Cell Biology, 2014Co-Authors: Michael N Conrad, David B Kaback, Michael E Dresser, Makkuni JayaramAbstract:The chromosome-like mitotic stability of the yeast 2 micron plasmid is conferred by the plasmid proteins Rep1-Rep2 and the cis-acting locus STB, likely by promoting plasmid-chromosome association and segregation by hitchhiking. Our analysis reveals that stable plasmid segregation during meiosis requires the bouquet proteins Ndj1 and Csm4. Plasmid relocalization from the nuclear interior in mitotic cells to the periphery at or proximal to telomeres rises from early meiosis to pachytene. Analogous to chromosomes, the plasmid undergoes Csm4- and Ndj1-dependent rapid prophase movements with speeds comparable to those of telomeres. Lack of Ndj1 partially disrupts plasmid–telomere association without affecting plasmid colocalization with the telomere-binding protein Rap1. The plasmid appears to engage a meiosis-specific motor that orchestrates telomere-led chromosome movements for its telomere-associated segregation during meiosis I. This hitherto uncharacterized mode of germ-line transmission by a Selfish genetic element signifies a mechanistic variation within the shared theme of chromosome-coupled plasmid segregation during mitosis and meiosis.
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yeast cohesin complex embraces 2 micron plasmid sisters in a tri linked catenane complex
Nucleic Acids Research, 2010Co-Authors: Santanu Kumar Ghosh, Chuchun Huang, Sujata Hajra, Makkuni JayaramAbstract:Sister chromatid cohesion, crucial for faithful segregation of replicated chromosomes in eukaryotes, is mediated by the multi-subunit protein complex cohesin. The Saccharomyces cerevisiae plasmid 2 micron circle mimics chromosomes in assembling cohesin at its partitioning locus. The plasmid is a multi-copy Selfish DNA element that resides in the nucleus and propagates itself stably, presumably with assistance from cohesin. In metaphase cell lysates, or fractions enriched for their cohesed state by sedimentation, plasmid molecules are trapped topologically by the protein ring formed by cohesin. They can be released from cohesin’s embrace either by linearizing the DNA or by cleaving a cohesin subunit. Assays using two distinctly tagged cohesin molecules argue against the hand-cuff (an associated pair of monomeric cohesin rings) or the bracelet (a dimeric cohesin ring) model as responsible for establishing plasmid cohesion. Our cumulative results most easily fit a model in which a single monomeric cohesin ring, rather than a series of such rings, conjoins a pair of sister plasmids. These features of plasmid cohesion account for its sister-to-sister mode of segregation by cohesin disassembly during anaphase. The mechanistic similarities of cohesion between mini-chromosome sisters and 2 micron plasmid sisters suggest a potential kinship between the plasmid partitioning locus and centromeres.
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Stable propagation of 'Selfish' genetic elements.
Journal of Biosciences, 2003Co-Authors: Soundarapandian Velmurugan, Shwetal Mehta, Dina Uzri, Makkuni JayaramAbstract:Extrachromosomal or chromosomally integrated genetic elements are common among prokaryotic and eukaryotic cells. These elements exhibit a variety of ‘Selfish’ strategies to ensure their replication and propagation during the growth of their host cells. To establish long-term persistence, they have to moderate the degree of Selfishness so as not to imperil the fitness of their hosts. Earlier genetic and biochemical studies together with more recent cell biological investigations have revealed details of the partitioning mechanisms employed by low copy bacterial plasmids. At least some bacterial chromosomes also appear to rely on similar mechanisms for their own segregation. The 2 μm plasmid ofSaccharomyces cerevisiae and related yeast plasmids provide models for optimized eukaryotic Selfish DNA elements. Selfish DNA elements exploit the genetic endowments of their hosts without imposing an undue metabolic burden on them. The partitioning systems of these plasmids appear to make use of a molecular trick by which the plasmids feed into the segregation pathway established for the host chromosomes.
David R Edgell - One of the best experts on this subject based on the ideXlab platform.
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Learning to live together: mutualism between self-splicing introns and their hosts
BMC Biology, 2011Co-Authors: David R Edgell, Venkata R. Chalamcharla, Marlene BelfortAbstract:Group I and II introns can be considered as molecular parasites that interrupt protein-coding and structural RNA genes in all domains of life. They function as self-splicing ribozymes and thereby limit the phenotypic costs associated with disruption of a host gene while they act as mobile DNA elements to promote their spread within and between genomes. Once considered purely Selfish DNA elements, they now seem, in the light of recent work on the molecular mechanisms regulating bacterial and phage group I and II intron dynamics, to show evidence of co-evolution with their hosts. These previously underappreciated relationships serve the co-evolving entities particularly well in times of environmental stress.
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Selfish DNA homing endonucleases find a home
Current Biology, 2009Co-Authors: David R EdgellAbstract:Summary Self-splicing group I introns come in two flavours — those with a homing endonuclease to promote mobility of the intron, and those without an endonuclease. How homing endonucleases and self-splicing introns associate to form a composite Selfish genetic element is a question of long-standing interest. Recent work has revealed that a shared characteristic of both introns and endonucleases, the targeting of conserved sequences, may provide the impetus for the evolution of composite mobile genetic elements.
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Selfish DNA new abode for homing endonucleases
Current Biology, 2002Co-Authors: David R EdgellAbstract:Abstract A 30-year old conundrum concerning the genetics of T-even bacteriophages has at last been solved, the answer turning out to involve free-standing homologs of intron-encoded homing endonucleases.
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Selfish DNA the best defense is a good offense
Current Biology, 1996Co-Authors: David R Edgell, Naomi M Fast, Ford W DoolittleAbstract:Abstract The recent discovery of novel biochemical activities of intron-encoded endonucleases emphasizes the Selfish nature of mobile genetic elements.
Eric U Selker - One of the best experts on this subject based on the ideXlab platform.
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Genome Defense: The Neurospora Paradigm
Epigenomics, 2020Co-Authors: Michael R. Rountree, Eric U SelkerAbstract:Eukaryotes deploy an array of defensive mechanisms to limit the destructive effects of “Selfish” DNA. These protective mechanisms include both transcriptional gene silencing (TGS) and RNA-based post-transcriptional gene silencing (PTGS) mechanisms. The filamentous fungus Neurospora crassa defends its genome with incredible tenacity utilizing two TGS mechanisms, repeat-induced point mutation (RIP) and DNA methylation and two PTGS mechanisms, quelling and meiotic silencing of unpaired DNA (MSUD).
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the dmm complex prevents spreading of DNA methylation from transposons to nearby genes in neurospora crassa
Genes & Development, 2010Co-Authors: Shinji Honda, Zachary A Lewis, Maite Huarte, Larry L David, Eric U SelkerAbstract:Transposable elements are common in genomes and must be controlled. Many organisms use DNA methylation to silence such Selfish DNA, but the mechanisms that restrict the methylation to appropriate regions are largely unknown. We identified a JmjC domain protein in Neurospora, DNA METHYLATION MODULATOR-1 (DMM-1), that prevents aberrant spreading of DNA and histone H3K9 methylation from inactivated transposons into nearby genes. Mutation of a conserved residue within the JmjC Fe(II)-binding site abolished dmm-1 function, as did mutations in conserved cysteine-rich domains. Mutants defective only in dmm-1 mutants grow poorly, but growth is restored by reduction or elimination of DNA methylation using the drug 5-azacytosine or by mutation of the DNA methyltransferase gene dim-2. DMM-1 relies on an associated protein, DMM-2, which bears a DNA-binding motif, for localization and proper function. HP1 is required to recruit the DMM complex to the edges of methylated regions.
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RIP: the evolutionary cost of genome defense.
Trends in Genetics, 2004Co-Authors: James E Galagan, Eric U SelkerAbstract:Repeat-induced point mutation (RIP) is a homology-based process that mutates repetitive DNA and frequently leads to epigenetic silencing of the mutated sequences through DNA methylation. Consistent with the hypothesis that RIP serves to control Selfish DNA, an analysis of the Neurospora crassa genome sequence reveals a complete absence of intact mobile elements. As in most eukaryotes, the centromeric regions of N. crassa are rich in sequences that are related to transposable elements; however, in N crassa these sequences have been heavily mutated. The analysis of the N. crassa genome sequence also reveals that RIP has impacted genome evolution significantly through gene duplication, which is considered to be crucial for the evolution of new functions. Most if not all paralogs in N. crassa duplicated and diverged before the emergence of RIP. Thus, RIP illustrates the extraordinary extent to which genomes will go to defend themselves against mobile genetic elements.
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RIP: The evolutionary cost of genome defense
Trends in Genetics, 2004Co-Authors: James E Galagan, Eric U SelkerAbstract:Repeat-induced point mutation (RIP) is a homology-based process that mutates repetitive DNA and frequently leads to epigenetic silencing of the mutated sequences through DNA methylation. Consistent with the hypothesis that RIP serves to control Selfish DNA, an analysis of the Neurospora crassa genome sequence reveals a complete absence of intact mobile elements. As in most eukaryotes, the centromeric regions of N. crassa are rich in sequences that are related to transposable elements; however, in N crassa these sequences have been heavily mutated. The analysis of the N. crassa genome sequence also reveals that RIP has impacted genome evolution significantly through gene duplication, which is considered to be crucial for the evolution of new functions. Most if not all paralogs in N. crassa duplicated and diverged before the emergence of RIP. Thus, RIP illustrates the extraordinary extent to which genomes will go to defend themselves against mobile genetic elements. © 2004 Elsevier Ltd.
Pierre Capy - One of the best experts on this subject based on the ideXlab platform.
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Genome ecosystem and transposable elements species.
Gene, 2007Co-Authors: Arnaud Le Rouzic, Stéphane Dupas, Pierre CapyAbstract:Transposable elements are known to be “Selfish DNA” sequences able to spread and be maintained in all genomes analyzed so far. Their evolution depends on the interaction they have with the other components of the genome, including genes and other transposable elements. These relationships are complex and have often been compared to those of species living and competing in an ecosystem. The aim of this current work is a proposition to fill the conceptual gap existing between genome biology and ecology, assuming that genomic components, such as transposable elements families, can be compared to species interacting in an ecosystem. Using this framework, some of the main models defined in the population genetics of transposable elements can then been reformulated, and some new kinds of realistic relationships, such as symbiosis between different genomic components, can then be modelled and explored.
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Theoretical Approaches to the Dynamics of Transposable Elements in Genomes, Populations, and Species
Transposons and the Dynamic Genome, 2006Co-Authors: Arnaud Le Rouzic, Pierre CapyAbstract:Transposable elements are major components of both prokaryotic and eukaryotic genomes. They are generally considered as “Selfish DNA” sequences able to invade the chromosomes of a species in a parasitic way, leading to a plethora of mutations such as insertions, deletions, inversions, translocations and complex rearrangements. They are frequently deleterious, but sometimes provide a source of genetic diversity. Numerous population genetics models have been proposed to describe more precisely the dynamics of these complex genomic components, and despite a wide diversity among transposable elements and their hosts, the colonization process appears to be roughly predictable. In this paper, we aim to describe and comment on some of the theoretical studies, and attempt to define the “life cycle” of these genomic nomads. We further raise some new issues about the impact of moving sequences in the evolution and the structure of genomes.
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the first steps of transposable elements invasion parasitic strategy vs genetic drift
Genetics, 2005Co-Authors: Arnaud Le Rouzic, Pierre CapyAbstract:Transposable elements are often considered as Selfish DNA sequences able to invade the genome of their host species. Their evolutive dynamics are complex, due to the interaction between their intrinsic amplification capacity, selection at the host level, transposition regulation, and genetic drift. Here, we propose modeling the first steps of TE invasion, i.e., just after a horizontal transfer, when a single copy is present in the genome of one individual. If the element has a constant transposition rate, it will disappear in most cases: the elements with low-transposition rate are frequently lost through genetic drift, while those with high-transposition rate may amplify, leading to the sterility of their host. Elements whose transposition rate is regulated are able to successfully invade the populations, thanks to an initial transposition burst followed by a strong limitation of their activity. Self-regulation or hybrid dysgenesis may thus represent some genome-invasion parasitic strategies.
Ford W Doolittle - One of the best experts on this subject based on the ideXlab platform.
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Selfish DNA the best defense is a good offense
Current Biology, 1996Co-Authors: David R Edgell, Naomi M Fast, Ford W DoolittleAbstract:Abstract The recent discovery of novel biochemical activities of intron-encoded endonucleases emphasizes the Selfish nature of mobile genetic elements.
