The Experts below are selected from a list of 2718 Experts worldwide ranked by ideXlab platform
Irene Chiolo - One of the best experts on this subject based on the ideXlab platform.
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arp2 3 and unc45 maintain heterochromatin stability in drosophila polytene chromosomes
Experimental Biology and Medicine, 2019Co-Authors: George Dialynas, Laetitia Delabaere, Irene ChioloAbstract:Repairing DNA double-strand breaks is particularly challenging in pericentromeric heterochromatin, where the abundance of repeated sequences exacerbates the risk of Ectopic Recombination. In Drosop...
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Arp2/3 and Unc45 maintain heterochromatin stability in Drosophila polytene chromosomes.
Experimental Biology and Medicine, 2019Co-Authors: George Dialynas, Laetitia Delabaere, Irene ChioloAbstract:Repairing DNA double-strand breaks is particularly challenging in pericentromeric heterochromatin, where the abundance of repeated sequences exacerbates the risk of Ectopic Recombination. In Drosop...
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arp2 3 and unc45 maintain heterochromatin stability in drosophila polytene chromosomes
bioRxiv, 2019Co-Authors: George Dialynas, Laetitia Delabaere, Irene ChioloAbstract:Repairing DNA double-strand breaks (DSBs) is particularly challenging in pericentromeric heterochromatin, where the abundance of repeated sequences exacerbates the risk of Ectopic Recombination. In Drosophila Kc cells, accurate homologous Recombination (HR) repair of heterochromatic DSBs relies on the relocalization of repair sites to the nuclear periphery before Rad51 recruitment and strand invasion. This movement is driven by Arp2/3-dependent nuclear actin filaments and myosins9 ability to walk along them. Conserved mechanisms enable the relocalization of heterochromatic DSBs in mouse cells, and their defects lead to massive Ectopic Recombination in heterochromatin and chromosome rearrangements. In Drosophila polytene chromosomes, extensive DNA movement is blocked by a stiff structure of chromosome bundles. Repair pathways in this context are poorly characterized, and whether heterochromatic DSBs relocalize in these cells is unknown. Here, we show that damage in heterochromatin results in relaxation of the heterochromatic chromocenter, consistent with a dynamic response in this structure. Arp2/3, the Arp2/3 activator Scar, and the myosin activator Unc45, are required for heterochromatin stability in polytene cells, suggesting that relocalization enables heterochromatin repair in this tissue. Together, these studies reveal critical roles for actin polymerization and myosin motors in heterochromatin repair and genome stability across different organisms and tissue types.
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Arp2/3 and Unc45 maintain heterochromatin stability in Drosophila polytene chromosomes
bioRxiv, 2019Co-Authors: George Dialynas, Laetitia Delabaere, Irene ChioloAbstract:Repairing DNA double-strand breaks (DSBs) is particularly challenging in pericentromeric heterochromatin, where the abundance of repeated sequences exacerbates the risk of Ectopic Recombination. In Drosophila Kc cells, accurate homologous Recombination (HR) repair of heterochromatic DSBs relies on the relocalization of repair sites to the nuclear periphery before Rad51 recruitment and strand invasion. This movement is driven by Arp2/3-dependent nuclear actin filaments and myosins9 ability to walk along them. Conserved mechanisms enable the relocalization of heterochromatic DSBs in mouse cells, and their defects lead to massive Ectopic Recombination in heterochromatin and chromosome rearrangements. In Drosophila polytene chromosomes, extensive DNA movement is blocked by a stiff structure of chromosome bundles. Repair pathways in this context are poorly characterized, and whether heterochromatic DSBs relocalize in these cells is unknown. Here, we show that damage in heterochromatin results in relaxation of the heterochromatic chromocenter, consistent with a dynamic response in this structure. Arp2/3, the Arp2/3 activator Scar, and the myosin activator Unc45, are required for heterochromatin stability in polytene cells, suggesting that relocalization enables heterochromatin repair in this tissue. Together, these studies reveal critical roles for actin polymerization and myosin motors in heterochromatin repair and genome stability across different organisms and tissue types.
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Nuclear Dynamics of Heterochromatin Repair
Trends in Genetics, 2017Co-Authors: Nuno Amaral, Taehyun Ryu, Irene ChioloAbstract:Repairing double-strand breaks (DSBs) is particularly challenging in pericentromeric heterochromatin, where the abundance of repeated sequences exacerbates the risk of Ectopic Recombination and chromosome rearrangements. Recent studies in Drosophila cells revealed that faithful homologous Recombination (HR) repair of heterochromatic DSBs relies on the relocalization of DSBs to the nuclear periphery before Rad51 recruitment. We summarize here the exciting progress in understanding this pathway, including conserved responses in mammalian cells and surprising similarities with mechanisms in yeast that deal with DSBs in distinct sites that are difficult to repair, including other repeated sequences. We will also point out some of the most important open questions in the field and emerging evidence suggesting that deregulating these pathways might have dramatic consequences for human health.
Martin Kupiec - One of the best experts on this subject based on the ideXlab platform.
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Characterization of the role played by the RAD59 gene of Saccharomyces cerevisiae in Ectopic Recombination
Current Genetics, 1999Co-Authors: Zehavit Jablonovich, Rivka Steinlauf, Batia Liefshitz, Martin KupiecAbstract:The RAD52 group of genes in the yeast Saccharomyces cerevisiae controls the repair of DNA damage by a Recombinational mechanism. Despite the growing evidence for physical and biochemical interactions between the proteins of this repair group, mutations in individual genes show very different effects on various types of Recombination. The RAD59 gene encodes a protein with similarity to Rad52p which plays a role in the repair of damage caused by ionizing radiation. In the present study we have examined the role played by the Rad59 protein in mitotic Ectopic Recombination and analyzed the genetic interactions with other members of the repair group. We found that Rad59p plays a role in Ectopic gene conversion that depends on the presence of Rad52p but is independent of the function of the RecA homologue Rad51p and of the Rad57 protein. The RAD59 gene product also participates in the RAD1-dependent pathway of Recombination between direct repeats. We propose that Rad59p may act in a salvage mechanism that operates when the Rad51 filament is not functional.
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Damage-induced Ectopic Recombination in the yeast Saccharomyces cerevisiae
Mutation Research-dna Repair, 1997Co-Authors: Martin Kupiec, Rivka SteinlaufAbstract:Mitotic Recombination in the yeast Saccharomyces cerevisiae is induced when cells are irradiated with UV or X-rays, reflecting the efficient repair of damage by Recombinational repair mechanisms. We have used multiply marked haploid strains that allow the simultaneous detection of several types of Ectopic Recombination events. We show that inter-chromosomal Ectopic conversion of lys2 heteroalleles and, to a lesser extent, direct repeat Recombination (DRR) between non-tandem repeats, are increased by DNA-damaging agents; in contrast, Ectopic Recombination of the naturally occurring Ty element is not induced. We have tested several hypotheses that could explain the preferential lack of induction of Ty Recombination by DNA-damaging agents. We have found that the lack of induction cannot be explained by a cell cycle control or by an effect of the mating-type genes. We also found no role for the flanking long terminal repeats (LTRs) of the Ty in preventing the induction. Ectopic conversion, DRR, and forward mutation of artificial repeats show different kinetics of induction at various positions of the cell cycle, reflecting different mechanisms of Recombination. We discuss the mechanistic and evolutionary aspects of these results.
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Induction of Ty Recombination in yeast by cDNA and transcription: role of the RAD1 and RAD52 genes.
Genetics, 1996Co-Authors: Yael Nevo-caspi, Martin KupiecAbstract:In the yeast Saccharomyces cerevisiae Ectopic Recombination has been shown to occur at high frequencies for artificially created repeats, but at relatively low frequencies for a natural family of repeated sequences, the Ty family. Little is known about the mechanism(s) that prevent Recombination between repeated sequences. We have previously shown that nonreciprocal Recombination (gene conversion) of a genetically marked Ty can be induced either by the presence of high levels of Ty cDNA or by transcription of the marked Ty from a GAL1 promoter. These two kinds of induction act in a synergistic manner. To further characterize these two kinds of Ty Recombination, we have investigated the role played by the RAD52 and RAD1 genes. We have found that the RAD52 and RAD1 gene products are essential to carry out transcription-induced Ty conversion whereas cDNA-mediated conversion can take place in their absence.
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Ectopic Recombination between Ty elements in Saccharomyces cerevisiae is not induced by DNA damage.
Molecular and Cellular Biology, 1992Co-Authors: Anat Parket, Martin KupiecAbstract:Mitotic Recombination is increased when cells are treated with a variety of physical and chemical agents that cause damage to their DNA. We show here, using Saccharomyces cerevisiae strains that carry marked Ty elements, that Recombination between members of this family of retrotransposons is not increased by UV irradiation or by treatment with the radiomimetic drug methyl methanesulfonate. Both Ectopic Recombination and mutation events were elevated by these agents for non-Ty sequences in the same strain. We discuss possible mechanisms that can prevent the induction of Recombination between Ty elements.
Alfredo Ruiz - One of the best experts on this subject based on the ideXlab platform.
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Structural and sequence diversity of the transposon Galileo in the Drosophila willistoni genome
BMC Genomics, 2014Co-Authors: Juliana W. Gonçalves, Alejandra Delprat, Victor Hugo Valiati, Vera L. S. Valente, Alfredo RuizAbstract:Background Galileo is one of three members of the P superfamily of DNA transposons. It was originally discovered in Drosophila buzzatii, in which three segregating chromosomal inversions were shown to have been generated by Ectopic Recombination between Galileo copies. Subsequently, Galileo was identified in six of 12 sequenced Drosophila genomes, indicating its widespread distribution within this genus. Galileo is strikingly abundant in Drosophila willistoni, a neotropical species that is highly polymorphic for chromosomal inversions, suggesting a role for this transposon in the evolution of its genome.
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The transposon Galileo generates natural chromosomal inversions in Drosophila by Ectopic Recombination.
PLOS ONE, 2009Co-Authors: Alejandra Delprat, Bárbara Negre, Marta Sabariego Puig, Alfredo RuizAbstract:Background Transposable elements (TEs) are responsible for the generation of chromosomal inversions in several groups of organisms. However, in Drosophila and other Dipterans, where inversions are abundant both as intraspecific polymorphisms and interspecific fixed differences, the evidence for a role of TEs is scarce. Previous work revealed that the transposon Galileo was involved in the generation of two polymorphic inversions of Drosophila buzzatii. Methodology/Principal Findings To assess the impact of TEs in Drosophila chromosomal evolution and shed light on the mechanism involved, we isolated and sequenced the two breakpoints of another widespread polymorphic inversion from D. buzzatii, 2z3. In the non inverted chromosome, the 2z3 distal breakpoint was located between genes CG2046 and CG10326 whereas the proximal breakpoint lies between two novel genes that we have named Dlh and Mdp. In the inverted chromosome, the analysis of the breakpoint sequences revealed relatively large insertions (2,870-bp and 4,786-bp long) including two copies of the transposon Galileo (subfamily Newton), one at each breakpoint, plus several other TEs. The two Galileo copies: (i) are inserted in opposite orientation; (ii) present exchanged target site duplications; and (iii) are both chimeric. Conclusions/Significance Our observations provide the best evidence gathered so far for the role of TEs in the generation of Drosophila inversions. In addition, they show unequivocally that Ectopic Recombination is the causative mechanism. The fact that the three polymorphic D. buzzatii inversions investigated so far were generated by the same transposon family is remarkable and is conceivably due to Galileo's unusual structure and current (or recent) transpositional activity.
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Generation of a Widespread Drosophila Inversion by a Transposable Element
Science, 1999Co-Authors: Mario Cáceres, José M. Ranz, Antonio Barbadilla, Manyuan Long, Alfredo RuizAbstract:Although polymorphic inversions in Drosophila are very common, the origin of these chromosomal rearrangements is unclear. The breakpoints of the cosmopolitan inversion 2j of D. buzzatii were cloned and sequenced. Both breakpoints contain large insertions corresponding to a transposable element. It appears that the two pairs of target site duplications generated upon insertion were exchanged during the inversion event, and that the inversion arose by Ectopic Recombination between two copies of the transposon that were in opposite orientations. This is apparently the mechanism by which transposable elements generate natural inversions in Drosophila.
Michael Lichten - One of the best experts on this subject based on the ideXlab platform.
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Compartmentalization of the yeast meiotic nucleus revealed by analysis of Ectopic Recombination
Genetics, 2004Co-Authors: Hélène B. Schlecht, Michael Lichten, Alastair S. H. GoldmanAbstract:As yeast cells enter meiosis, chromosomes move from a centromere-clustered (Rabl) to a telomere-clustered (bouquet) configuration and then to states of progressive homolog pairing where telomeres are more dispersed. It is uncertain at which stage of this process sequences commit to recombine with each other. Previous analyses using Recombination between dispersed homologous sequences (Ectopic Recombination) support the view that, on average, homologs are aligned end to end by the time of commitment to Recombination. We have undertaken further analyses incorporating new inserts, chromosome rearrangements, an alternate mode of Recombination initiation, and mutants that disrupt nuclear structure or telomere metabolism. Our findings support previous conclusions and reveal that distance from the nearest telomere is an important parameter influencing Recombination between dispersed sequences. In general, the farther dispersed sequences are from their nearest telomere, the less likely they are to engage in Ectopic Recombination. Neither the mode of initiating Recombination nor the formation of the bouquet appears to affect this relationship. We suggest that aspects of telomere localization and behavior influence the organization and mobility of chromosomes along their entire length, during a critical period of meiosis I prophase that encompasses the homology search.
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Restriction of Ectopic Recombination by interhomolog interactions during Saccharomyces cerevisiae meiosis
Proceedings of the National Academy of Sciences of the United States of America, 2000Co-Authors: Alastair S. H. Goldman, Michael LichtenAbstract:In Saccharomyces cerevisiae meiosis, Recombination occurs frequently between sequences at the same location on homologs (allelic Recombination) and can take place between dispersed homologous sequences (Ectopic Recombination). Ectopic Recombination occurs less often than does allelic, especially when homologous sequences are on heterologous chromosomes. To account for this, it has been suggested that homolog pairing (homolog colocalization and alignment) either promotes allelic Recombination or restricts Ectopic Recombination. The latter suggestion was tested by examining Ectopic Recombination in two cases where normal interhomolog relationships are disrupted. In the first case, one member of a homolog pair was replaced by a homoeologous (related but not identical) chromosome that has diverged sufficiently to prevent allelic Recombination. In the second case, ndj1 mutants were used to delay homolog pairing and synapsis. Both circumstances resulted in a substantial increase in the frequency of Ectopic Recombination between arg4-containing plasmid inserts located on heterologous chromosomes. These findings suggest that, during normal yeast meiosis, progressive homolog colocalization, alignment, synapsis, and allelic Recombination restrict the ability of Ectopically located sequences to find each other and recombine. In the absence of such restrictions, the meiotic homology search may encompass the entire genome.
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Saccharomyces cerevisiae checkpoint genes MEC1, RAD17 and RAD24 are required for normal meiotic Recombination partner choice.
Genetics, 1999Co-Authors: Jeremy M. Grushcow, Michael Lichten, Teresa M. Holzen, Ken J. Park, Ted Weinert, Douglas K. BishopAbstract:Checkpoint gene function prevents meiotic progression when Recombination is blocked by mutations in the recA homologue DMC1. Bypass of dmc1 arrest by mutation of the DNA damage checkpoint genes MEC1, RAD17, or RAD24 results in a dramatic loss of spore viability, suggesting that these genes play an important role in monitoring the progression of Recombination. We show here that the role of mitotic checkpoint genes in meiosis is not limited to maintaining arrest in abnormal meioses; mec1-1, rad24, and rad17 single mutants have additional meiotic defects. All three mutants display Zip1 polycomplexes in two- to threefold more nuclei than observed in wild-type controls, suggesting that synapsis may be aberrant. Additionally, all three mutants exhibit elevated levels of Ectopic Recombination in a novel physical assay. rad17 mutants also alter the fraction of Recombination events that are accompanied by an exchange of flanking markers. Crossovers are associated with up to 90% of Recombination events for one pair of alleles in rad17, as compared with 65% in wild type. Meiotic progression is not required to allow Ectopic Recombination in rad17 mutants, as it still occurs at elevated levels in ndt80 mutants that arrest in prophase regardless of checkpoint signaling. These observations support the suggestion that MEC1, RAD17, and RAD24, in addition to their proposed monitoring function, act to promote normal meiotic Recombination.
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The efficiency of meiotic Recombination between dispersed sequences in Saccharomyces cerevisiae depends upon their chromosomal location
Genetics, 1996Co-Authors: Alastair S. H. Goldman, Michael LichtenAbstract:To examine constraints imposed on meiotic Recombination by homologue pairing, we measured the frequency of Recombination between mutant alleles of the ARG4 gene contained in pBR322-based inserts. Inserts were located at identical loci on homologues (allelic Recombination) or at different loci on either homologous or heterologous chromosomes (Ectopic Recombination). Ectopic Recombination between interstitially located inserts on heterologous chromosomes had an efficiency of 6-12% compared to allelic Recombination. By contrast, Ectopic Recombination between interstitial inserts located on homologues had relative efficiencies of 47-99%. These findings suggest that when meiotic Ectopic Recombination occurs, homologous chromosomes are already colocalized. The efficiency of Ectopic Recombination between inserts on homologues decreased as the physical distance between insert sites was increased. This result is consistent with the suggestion that during meiotic Recombination, homologues are not only close to each other, but also are aligned end to end. Finally, the efficiency of Ectopic Recombination between inserts near telomeres (within 16 kb) was significantly greater than that observed with inserts >50 kb from the nearest telomere. Thus, at the time of Recombination, there may be a special relationship between the ends of chromosomes not shared with interstitial regions.
Eduard Kejnovsky - One of the best experts on this subject based on the ideXlab platform.
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What Can Long Terminal Repeats Tell Us About the Age of LTR Retrotransposons, Gene Conversion and Ectopic Recombination?
Frontiers in Plant Science, 2020Co-Authors: Pavel Jedlička, Matej Lexa, Eduard KejnovskyAbstract:LTR retrotransposons constitute a significant part of plant genomes and their evolutionary dynamics play an important role in genome size changes. Current methods of LTR retrotransposon age estimation are based only on LTR (long terminal repeat) divergence. This has prompted us to analyse sequence similarity of LTRs in 25,144 LTR retrotransposons from fifteen plant species. as well as formation of solo LTRs. We found that approximately one fourth of nested retrotransposons showed a higher LTR divergence than the pre-existing retrotransposons into which they had been inserted. Moreover, LTR similarity was correlated with LTR length. We propose that gene conversion can contribute to this phenomenon. Gene conversion prediction in LTRs showed potential converted regions in 25 % of LTR pairs. Gene conversion was higher in species with smaller genomes while the proportion of solo LTRs did not change with genome size in analyzed species. The negative correlation between the extent of gene conversion and the abundance of solo LTRs suggests interference between gene conversion and Ectopic Recombination. Since such phenomena limit the traditional methods of LTR retrotransposon age estimation, we recommend an improved approach based on the exclusion of regions affected by gene conversion.
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Impact of repetitive DNA on sex chromosome evolution in plants.
Chromosome Research, 2015Co-Authors: Roman Hobza, Zdenek Kubat, Radim Cegan, Wojciech Jesionek, Boris Vyskot, Eduard KejnovskyAbstract:Structurally and functionally diverged sex chromosomes have evolved in many animals as well as in some plants. Sex chromosomes represent a specific genomic region(s) with locally suppressed Recombination. As a consequence, repetitive sequences involving transposable elements, tandem repeats (satellites and microsatellites), and organellar DNA accumulate on the Y (W) chromosomes. In this paper, we review the main types of repetitive elements, their gathering on the Y chromosome, and discuss new findings showing that not only accumulation of various repeats in non-recombining regions but also opposite processes form Y chromosome. The aim of this review is also to discuss the mechanisms of repetitive DNA spread involving (retro) transposition, DNA polymerase slippage or unequal crossing-over, as well as modes of repeat removal by Ectopic Recombination. The intensity of these processes differs in non-recombining region(s) of sex chromosomes when compared to the recombining parts of genome. We also speculate about the relationship between heterochromatinization and the formation of heteromorphic sex chromosomes.
