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Alain Nicolas - One of the best experts on this subject based on the ideXlab platform.
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Identification of determining factors for Meiotic Recombination targeting in bread wheat
2017Co-Authors: Robin Michard, Alain Nicolas, Marie-claire Debote, Caroline Tassy, Giacomo Bastianelli, Pierre Barret, Pierre SourdilleAbstract:Identification of determining factors for Meiotic Recombination targeting in bread wheat. 12. French 3R Meeting
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Targeted Stimulation of Meiotic Recombination
Cell, 2002Co-Authors: Ana Peciña, Kunihiro Ohta, Christine Mézard, Kathleen Smith, Hajime Murakami, Alain NicolasAbstract:Meiotic Recombination in Saccharomyces cerevisiae is initiated by programmed DNA double-strand breaks (DSBs), a process that requires the Spo11 protein. DSBs usually occur in intergenic regions that display open chromatin accessibility, but other determinants that control their frequencies and non-random chromosomal distribution remain obscure. We report that a Spo11 construct bearing the Gal4 DNA binding domain not only rescues spo11Delta spore inviability and catalyzes DSB formation at natural sites but also strongly stimulates DSB formation near Gal4 binding sites. At GAL2, a naturally DSB-cold locus, Gal4BD-Spo11 creates a Recombinational hotspot that depends on all the other DSB gene functions, showing that the targeting of Spo11 to a specific site is sufficient to stimulate Meiotic Recombination that is under normal physiological control.
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Replication Protein A Is Required for Meiotic Recombination in Saccharomyces cerevisiae
Genetics, 2002Co-Authors: Christine Soustelle, Michele Vedel, Richard D. Kolodner, Alain NicolasAbstract:In Saccharomyces cerevisiae, Meiotic Recombination is initiated by transient DNA double-stranded breaks (DSBs). These DSBs undergo a 5' --> 3' resection to produce 3' single-stranded DNA ends that serve to channel DSBs into the RAD52 Recombinational repair pathway. In vitro studies strongly suggest that several proteins of this pathway--Rad51, Rad52, Rad54, Rad55, Rad57, and replication protein A (RPA)--play a role in the strand exchange reaction. Here, we report a study of the Meiotic phenotypes conferred by two missense mutations affecting the largest subunit of RPA, which are localized in the protein interaction domain (rfa1-t11) and in the DNA-binding domain (rfa1-t48). We find that both mutant diploids exhibit reduced sporulation efficiency, very poor spore viability, and a 10- to 100-fold decrease in Meiotic Recombination. Physical analyses indicate that both mutants form normal levels of meiosis-specific DSBs and that the broken ends are processed into 3'-OH single-stranded tails, indicating that the RPA complex present in these rfa1 mutants is functional in the initial steps of Meiotic Recombination. However, the 5' ends of the broken fragments undergo extensive resection, similar to what is observed in rad51, rad52, rad55, and rad57 mutants, indicating that these RPA mutants are defective in the repair of the Spo11-dependent DSBs that initiate homologous Recombination during meiosis.
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Mechanisms and control of Meiotic Recombination in the yeast Saccharomyces cerevisiae
Journal de la Societe de biologie, 1999Co-Authors: Christine Mézard, Kathleen Smith, Frédéric Baudat, Hélène Debrauwère, De Massy B, Christine Soustelle, Paul-christophe Varoutas, Michele Vedel, Alain NicolasAbstract:Recent studies in Saccharomyces cerevisiae have provided new insights in our understanding of the molecular mechanisms of Meiotic Recombination. Meiosis-specific DNA double-strand breaks have been detected and have been shown to be the lesions that initiate Recombination events. These are located mostly in promoter regions where the chromatin is in an open configuration, and cluster in domains along the chromosome. They are likely to be made by a topoisomerase II-like protein encoded by the SPO11 gene. Several DNA intermediates in the Meiotic double strand-break repair pathway have been characterised and several multi-protein complexes have been identified and shown to be involved at different steps in the repair pathway. The conservation of these protein complexes in higher eukaryotes suggests that the Meiotic Recombination mechanism could be conserved. With the application of the well characterised genetical, molecular, cytological and biochemical techniques and the recently developed technology for genomic studies (biochips), we can expect a rapid increase in our comprehension of the Meiotic Recombination process.
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Relationship between transcription and initiation of Meiotic Recombination: Toward chromatin accessibility
Proceedings of the National Academy of Sciences of the United States of America, 1998Co-Authors: Alain NicolasAbstract:Since the high level of Meiotic Recombination at the ARG4 locus of the budding yeast Saccharomyces cerevisiae was found to be controlled by a cis-acting initiator located within its 5′ noncoding region (1), the question of the relationship between transcription and Meiotic Recombination control was raised. Are promoters and sites at which Meiotic Recombination initiates functionally related? Transcription by RNA polymerase I and II appears to stimulate mitotic Recombination in S. cerevisiae (2, 3), but how is Meiotic Recombination affected by local gene expression? The paper by Kon et al. (4), in conjunction with other recent contributions concerning the M26 hot spot of Meiotic Recombination in the fission yeast Schizosaccharomyces pombe, provides compelling new insights and prompts additional questions. This commentary/mini-review will focus on the control of the initiation of Meiotic Recombination in these yeasts.
Alexander Lorenz - One of the best experts on this subject based on the ideXlab platform.
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Intragenic Meiotic Recombination in Schizosaccharomyces pombe is sensitive to environmental temperature changes
Chromosome Research, 2020Co-Authors: Simon D. Brown, Charlotte Audoynaud, Alexander LorenzAbstract:Changes in environmental temperature influence cellular processes and their dynamics, and thus affect the life cycle of organisms that are unable to control their cell/body temperature. Meiotic Recombination is the cellular process essential for producing healthy haploid gametes by providing physical links (chiasmata) between homologous chromosomes to guide their accurate segregation. Additionally, Meiotic Recombination—initiated by programmed DNA double-strand breaks (DSBs)—can generate genetic diversity and, therefore, is a driving force of evolution. Environmental temperature influencing Meiotic Recombination outcome thus may be a crucial determinant of reproductive success and genetic diversity. Indeed, Meiotic Recombination frequency in fungi, plants and invertebrates changes with temperature. In most organisms, these temperature-induced changes in Meiotic Recombination seem to be mediated through the meiosis-specific chromosome axis organization, the synaptonemal complex in particular. The fission yeast Schizosaccharomyces pombe does not possess a synaptonemal complex. Thus, we tested how environmental temperature modulates Meiotic Recombination frequency in the absence of a fully-fledged synaptonemal complex. We show that intragenic Recombination (gene conversion) positively correlates with temperature within a certain range, especially at Meiotic Recombination hotspots. In contrast, crossover Recombination, which manifests itself as chiasmata, is less affected. Based on our observations, we suggest that, in addition to changes in DSB frequency, DSB processing could be another temperature-sensitive step causing temperature-induced Recombination rate alterations.
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DNA sequence differences are determinants of Meiotic Recombination outcome.
Scientific reports, 2019Co-Authors: Simon D. Brown, Samantha J. Mpaulo, Mimi Nwakaego Asogwa, Marie Jézéquel, Matthew C. Whitby, Alexander LorenzAbstract:Meiotic Recombination is essential for producing healthy gametes, and also generates genetic diversity. DNA double-strand break (DSB) formation is the initiating step of Meiotic Recombination, producing, among other outcomes, crossovers between homologous chromosomes (homologs), which provide physical links to guide accurate chromosome segregation. The parameters influencing DSB position and repair are thus crucial determinants of reproductive success and genetic diversity. Using Schizosaccharomyces pombe, we show that the distance between sequence polymorphisms across homologs has a strong impact on Meiotic Recombination rate. The closer the sequence polymorphisms are to each other across the homologs the fewer Recombination events were observed. In the immediate vicinity of DSBs, sequence polymorphisms affect the frequency of intragenic Recombination events (gene conversions). Additionally, and unexpectedly, the crossover rate of flanking markers tens of kilobases away from the sequence polymorphisms was affected by their relative position to each other amongst the progeny having undergone intragenic Recombination. A major regulator of this distance-dependent effect is the MutSα-MutLα complex consisting of Msh2, Msh6, Mlh1, and Pms1. Additionally, the DNA helicases Rqh1 and Fml1 shape Recombination frequency, although the effects seen here are largely independent of the relative position of the sequence polymorphisms.
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dna sequence differences are determinants of Meiotic Recombination outcome
bioRxiv, 2019Co-Authors: Simon D. Brown, Samantha J. Mpaulo, Mimi Nwakaego Asogwa, Marie Jézéquel, Matthew C. Whitby, Alexander LorenzAbstract:Abstract Meiotic Recombination is essential for producing healthy gametes, and also generates genetic diversity. DNA double-strand break (DSB) formation is the initiating step of Meiotic Recombination, producing, among other outcomes, crossovers between homologous chromosomes (homologs), which provide physical links to guide accurate chromosome segregation. The parameters influencing DSB position and repair are thus crucial determinants of reproductive success and genetic diversity. Using Schizosaccharomyces pombe, we show that the distance between sequence polymorphisms across homologs has a strong impact on Meiotic Recombination rate. The closer the sequence polymorphisms are to each other across the homologs the fewer Recombination events were observed. In the immediate vicinity of DSBs sequence polymorphisms affect the frequency of intragenic Recombination events (gene conversions and intragenic crossovers). Additionally, and unexpectedly, the crossover rate of flanking markers tens of kilobases away from the sequence polymorphisms was affected by their relative position to each other amongst the progeny having undergone intragenic Recombination. A major regulator of this distance-dependent effect is the MutSα-MutLα complex consisting of Msh2, Msh6, Mlh1, and Pms1. Additionally, the DNA helicases Rqh1 and Fml1 shape Recombination frequency, although the effects seen here are largely independent of the relative position of the sequence polymorphisms.
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DNA sequence differences and temperature are determinants of Meiotic Recombination outcome
2019Co-Authors: Simon D. Brown, Charlotte Audoynaud, Samantha J. Mpaulo, Mimi Nwakaego Asogwa, Marie Jézéquel, Matthew C. Whitby, Alexander LorenzAbstract:Abstract Meiotic Recombination is essential for producing healthy gametes, and also generates genetic diversity. DNA double-strand break (DSB) formation is the initiating step of Meiotic Recombination, producing, among other outcomes, crossovers between homologous chromosomes (homologs), which provide physical links to guide accurate chromosome segregation. The parameters influencing DSB position and repair are thus crucial determinants of reproductive success and genetic diversity. Using Schizosaccharomyces pombe, we show that the distance between sequence polymorphisms across homologs has a strong impact on Meiotic Recombination rate. The closer the sequence polymorphisms are to each other across the homologs the fewer Recombination events were observed. In the immediate vicinity of DSBs sequence polymorphisms affect the frequency of intragenic Recombination events (gene conversions and intragenic crossovers). Additionally, and unexpectedly, the crossover rate of flanking markers tens of kilobases away from the sequence polymorphisms was affected by their relative position to each other amongst the progeny having undergone intragenic Recombination. A major regulator of this distance-dependent effect is the MutSα-MutLα complex consisting of Msh2, Msh6, Mlh1, and Pms1. Additionally, the DNA helicases Rqh1 and Fml1 shape Recombination frequency, although the effects seen here are largely independent of the relative position of the sequence polymorphisms.
Yingxiang Wang - One of the best experts on this subject based on the ideXlab platform.
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Meiotic Recombination: Mixing It Up in Plants.
Annual review of plant biology, 2018Co-Authors: Yingxiang Wang, Gregory P CopenhaverAbstract:Meiosis halves diploid chromosome numbers to haploid levels that are essential for sexual reproduction in most eukaryotes. Meiotic Recombination ensures the formation of bivalents between homologous chromosomes (homologs) and their subsequent proper segregation. It also results in genetic diversity among progeny that influences evolutionary responses to selection. Moreover, crop breeding depends upon the action of Meiotic Recombination to rearrange elite traits between parental chromosomes. An understanding of the molecular mechanisms that drive Meiotic Recombination is important for both fundamental research and practical applications. This review emphasizes advances made during the past 5 years, primarily in Arabidopsis and rice, by summarizing newly characterized genes and proteins and examining the regulatory mechanisms that modulate their action.
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arabidopsis rad51 rad51c and xrcc3 proteins form a complex and facilitate rad51 localization on chromosomes for Meiotic Recombination
PLOS Genetics, 2017Co-Authors: Hang Su, Gregory P Copenhaver, Jiyue Huang, Zhihao Cheng, Yingxiang WangAbstract:Meiotic Recombination is required for proper homologous chromosome segregation in plants and other eukaryotes. The eukaryotic RAD51 gene family has seven ancient paralogs with important roles in mitotic and Meiotic Recombination. Mutations in mammalian RAD51 homologs RAD51C and XRCC3 lead to embryonic lethality. In the model plant Arabidopsis thaliana, RAD51C and XRCC3 homologs are not essential for vegetative development but are each required for somatic and Meiotic Recombination, but the mechanism of RAD51C and XRCC3 in Meiotic Recombination is unclear. The non-lethal Arabidopsis rad51c and xrcc3 null mutants provide an opportunity to study their Meiotic functions. Here, we show that AtRAD51C and AtXRCC3 are components of the RAD51-dependent Meiotic Recombination pathway and required for normal AtRAD51 localization on Meiotic chromosomes. In addition, AtRAD51C interacts with both AtRAD51 and AtXRCC3 in vitro and in vivo, suggesting that these proteins form a complex (es). Comparison of AtRAD51 foci in meiocytes from atrad51, atrad51c, and atxrcc3 single, double and triple heterozygous mutants further supports an interaction between AtRAD51C and AtXRCC3 that enhances AtRAD51 localization. Moreover, atrad51c-/+ atxrcc3-/+ double and atrad51-/+ atrad51c-/+ atxrcc3-/+ triple heterozygous mutants have defects in Meiotic Recombination, suggesting the role of the AtRAD51C-AtXRCC3 complex in Meiotic Recombination is in part AtRAD51-dependent. Together, our results support a model in which direct interactions between the RAD51C-XRCC3 complex and RAD51 facilitate RAD51 localization on Meiotic chromosomes and RAD51-dependent Meiotic Recombination. Finally, we hypothesize that maintenance of RAD51 function facilitated by the RAD51C-XRCC3 complex could be highly conserved in eukaryotes.
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New insights into the role of DNA synthesis in Meiotic Recombination
Science Bulletin, 2016Co-Authors: Jiyue Huang, Gregory P Copenhaver, Yingxiang WangAbstract:Meiosis comprises two rounds of nuclear division following a single phase of DNA replication, leading to the production of haploid gametes and is essential for sexual reproduction in eukaryotes. Unlike mitosis, meiosis involves homologous chromosome pairing, synapsis, and Recombination during prophase I. Meiotic Recombination not only ensures the accurate segregation of homologs, but also redistributes alleles among offspring. DNA synthesis is a critical process during Meiotic Recombination, but our understanding of the proteins that execute and regulate it is limited. This review summarizes the recent advances in defining the role of DNA synthesis in Meiotic Recombination through analyses of DNA synthesis genes, with specific emphasis on DNA polymerases (e.g., Pole and Polδ), replication processivity factor RFC1 and translesion polymerases (e.g., Polζ). We also present a new double strand break repair model for Meiotic Recombination, which includes lagging strand DNA synthesis and leading strand elongation. Finally, we propose that DNA synthesis is one of critical factors for discriminating Meiotic Recombination pathways and that this differentiation may be conserved among eukaryotes.
Thomas D. Petes - One of the best experts on this subject based on the ideXlab platform.
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Meiotic Recombination hot spots and cold spots
Nature Reviews Genetics, 2001Co-Authors: Thomas D. PetesAbstract:Meiotic Recombination events are distributed unevenly throughout eukaryotic genomes. This inhomogeneity leads to distortions of genetic maps that can hinder the ability of geneticists to identify genes by map-based techniques. Various lines of evidence, particularly from studies of yeast, indicate that the distribution of Recombination events might reflect, at least in part, global features of chromosome structure, such as the distribution of modified nucleosomes.
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Competition Between Adjacent Meiotic Recombination Hotspots in the Yeast Saccharomyces cerevisiae
Genetics, 1997Co-Authors: Qing Qing Fan, Michael A. White, Thomas D. PetesAbstract:In a wild-type strain of Saccharomyces cerevisiae, a hotspot for Meiotic Recombination is located upstream of the HIS4 gene. An insertion of a 49-bp telomeric sequence into the coding region of HIS4 strongly stimulates Meiotic Recombination and the local formation of meiosis-specific double-strand DNA breaks (DSBs). When strains are constructed in which both hotspots are heterozygous, hotspot activity is substantially less when the hotspots are on the same chromosome than when they are on opposite chromosomes.
Scott Keeney - One of the best experts on this subject based on the ideXlab platform.
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ATR is required to complete Meiotic Recombination in mice.
Nature communications, 2018Co-Authors: Sarai Pacheco, Scott Keeney, Andros Maldonado-linares, Marina Marcet-ortega, Cristina Rojas, Ana Martínez-marchal, Judit Fuentes-lazaro, Julian Lange, Maria Jasin, Oscar Fernandez-capetilloAbstract:Precise execution of Recombination during meiosis is essential for forming chromosomally-balanced gametes. Meiotic Recombination initiates with the formation and resection of DNA double-strand breaks (DSBs). Cellular responses to Meiotic DSBs are critical for efficient repair and quality control, but molecular features of these remain poorly understood, particularly in mammals. Here we report that the DNA damage response protein kinase ATR is crucial for Meiotic Recombination and completion of Meiotic prophase in mice. Using a hypomorphic Atr mutation and pharmacological inhibition of ATR in vivo and in cultured spermatocytes, we show that ATR, through its effector kinase CHK1, promotes efficient RAD51 and DMC1 assembly at RPA-coated resected DSB sites and establishment of interhomolog connections during meiosis. Furthermore, our findings suggest that ATR promotes local accumulation of Recombination markers on unsynapsed axes during Meiotic prophase to favor homologous chromosome synapsis. These data reveal that ATR plays multiple roles in mammalian Meiotic Recombination.
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ATR Is Required To Complete Meiotic Recombination In Mice
2017Co-Authors: Sarai Pacheco, Scott Keeney, Andros Maldonado-linares, Marina Marcet-ortega, Cristina Rojas, Ana Martínez-marchal, Judit Fuentes-lazaro, Julian Lange, Maria Jasin, Oscar Fernandez-capetilloAbstract:Precise execution of Recombination during meiosis is essential for forming chromosomally balanced gametes. Meiotic Recombination initiates with the formation and resection of DNA double-strand breaks (DSBs). Binding of replication protein A (RPA) at resected DSBs fosters association of RAD51 and DMC1, the primary effectors of homology search. It is well appreciated that cellular responses to Meiotic DSBs are critical for efficient repair and quality control, but molecular features of these responses remain poorly understood, particularly in mammals. Here we provide evidence that the DNA damage response protein kinase ATR is crucial for Meiotic Recombination and completion of Meiotic prophase in mice. Using a hypomorphic Atr mutation and pharmacological inhibition of ATR in vivo and in cultured spermatocytes, we show that ATR, through its effector kinase CHK1, promotes efficient RAD51 and DMC1 assembly at RPA-coated DSB sites and establishment of interhomolog connections during meiosis. Furthermore, our findings suggest that ATR promotes local accumulation of Recombination markers on unsynapsed axes during Meiotic prophase to favor homologous chromosome synapsis. These data reveal that ATR plays multiple roles in mammalian Meiotic Recombination.
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Mechanism and regulation of Meiotic Recombination initiation
Cold Spring Harbor Perspectives in Biology, 2015Co-Authors: Isabel Lam, Scott KeeneyAbstract:Meiotic Recombination involves the formation and repair of programmed DNA double-strand breaks (DSBs) catalyzed by the conserved Spo11 protein. This review summarizes recent studies pertaining to the formation of Meiotic DSBs, including the mechanism of DNA cleavage by Spo11, proteins required for break formation, and mechanisms that control the location, timing, and number of DSBs. Where appropriate, findings in different organisms are discussed to highlight evolutionary conservation or divergence.
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Probing Meiotic Recombination Decisions
Developmental cell, 2008Co-Authors: Ignasi Roig, Scott KeeneyAbstract:Meiotic Recombination promotes genetic variation by mixing parental alleles. Two recent studies, one in this issue of Developmental Cell, have applied microarray-based methods that allow analysis of nearly all of the Recombination events occurring in a single meiosis. These data provide insights into the molecular "decisions" that control the outcome of the Recombination process.
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Meiotic Recombination: Making and breaking go hand in hand
Current biology : CB, 2001Co-Authors: Frédéric Baudat, Scott KeeneyAbstract:Accurate segregation of homologous chromosomes at the first Meiotic division requires the tight coordination of DNA replication, homologous Recombination and chromosome organization. Recent studies suggest that the initiation of Meiotic Recombination is mechanistically coupled to preMeiotic DNA replication.
