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Meiotic recombination

Ganga Anil Kumar, Kuppuswamy Subramaniam
Pairing of homologous chromosomes is essential for genetic recombination during gametogenesis. In many organisms, chromosome ends are attached to cytoplasmic dynein, and dynein-driven chromosomal movements facilitate the pairing process. Factors that promote / control the cytoskeletal tethering of chromosomes are largely unknown. Here, we show that the conserved RNA-binding protein PUF-8 facilitates the tethering and pairing processes in the C. elegans germline by promoting proteasome activity. We have isolated a hypomorphic allele of pas-1 , which encodes a proteasome core subunit, and find that the homologous chromosomes fail to pair in the puf-8; pas-1 double mutant due to failure of chromosome tethering...
March 14, 2018: Development
Sona Gregorova, Vaclav Gergelits, Irena Chvatalova, Tanmoy Bhattacharyya, Barbora Valiskova, Vladana Fotopulosova, Petr Jansa, Diana Wiatrowska, Jiri Forejt
Hybrid sterility is one of the reproductive isolation mechanisms leading to speciation. Prdm9 , the only known vertebrate hybrid sterility gene, causes failure of meiotic chromosome synapsis and infertility in male hybrids between two mouse subspecies. But within species Prdm9 determines the sites of programmed DNA double-strand breaks and meiotic recombination hotspots. To investigate the relation between Prdm9 -controlled meiotic arrest and asynapsis, we inserted random stretches of consubspecific homology on several autosomal pairs in sterile hybrids and analyzed their ability to form synaptonemal complexes and rescue male fertility...
March 14, 2018: ELife
Chunwei Ye, Yi Cai, Qian Cai, Shunhui Yuan, Fan Huang, Xiaofang Yang, Shuchen He, Zhuoheng Li, Yanwen Wang, Delin Yang, Zhipeng Li
The aim of the present study was to investigate the candidate genes and pathways associated with benign prostatic hyperplasia (BPH) and diabetes. In vitro experiments were performed using normal prostatic epithelial RWPE‑1 and HPr‑1 cells. The cell lines were treated with a high‑glucose solution and MTS and bromodeoxyuridine assays were used to assess cell viability. Transcriptome sequencing was used to screen the candidate genes. The expression of candidate genes was further verified by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blotting...
March 7, 2018: International Journal of Molecular Medicine
Kyuha Choi, Xiaohui Zhao, Andrew J Tock, Christophe Lambing, Charles J Underwood, Thomas J Hardcastle, Heïdi Serra, Juhyun Kim, Hyun Seob Cho, Jaeil Kim, Piotr A Ziolkowski, Nataliya E Yelina, Ildoo Hwang, Robert A Martienssen, Ian R Henderson
Meiotic recombination initiates from DNA double-strand breaks (DSBs) generated by SPO11 topoisomerase-like complexes. Meiotic DSB frequency varies extensively along eukaryotic chromosomes, with hotspots controlled by chromatin and DNA sequence. To map meiotic DSBs throughout a plant genome, we purified and sequenced Arabidopsis thaliana SPO11-1-oligonucleotides. SPO11-1-oligos are elevated in gene promoters, terminators, and introns, which is driven by AT-sequence richness that excludes nucleosomes and allows SPO11-1 access...
March 12, 2018: Genome Research
Charles J Underwood, Kyuha Choi, Christophe Lambing, Xiaohui Zhao, Heïdi Serra, Filipe Borges, Joe Simorowski, Evan Ernst, Yannick Jacob, Ian R Henderson, Robert A Martienssen
Eukaryotic centromeres contain the kinetochore, which connects chromosomes to the spindle allowing segregation. During meiosis, centromeres are suppressed for inter-homolog crossover, as recombination in these regions can cause chromosome missegregation and aneuploidy. Plant centromeres are surrounded by transposon-dense pericentromeric heterochromatin that is epigenetically silenced by histone 3 lysine 9 dimethylation (H3K9me2), and DNA methylation in CG and non-CG sequence contexts. However, the role of these chromatin modifications in control of meiotic recombination in the pericentromeres is not fully understood...
March 12, 2018: Genome Research
Kevin Brick, Florencia Pratto, Chi-Yu Sun, Rafael D Camerini-Otero, Galina Petukhova
The repair of programmed DNA double-strand breaks (DSBs) physically tethers homologous chromosomes in meiosis to allow for accurate segregation through meiotic cell divisions. This process, known as recombination, also results in the exchange of alleles between parental chromosomes and contributes to genetic diversity. In mammals, meiotic DSBs occur predominantly in a small fraction of the genome, at sites known as hotspots. Studies of the formation and repair of meiotic DSBs in mammals are challenging, because few cells undergo meiotic DSB formation at a given time...
2018: Methods in Enzymology
Hardeep Kaur, Jasvinder S Ahuja, Michael Lichten
Proteins with potential roles in meiotic recombination often have essential or important functions during the mitotic cell cycle. In addition, proteins may have different functions at different times during meiosis. In such cases, it can be challenging to precisely determine protein function during meiosis using null or hypomorphic mutants. One example is the Sgs1-Top3-Rmi1 helicase-decatenase complex, which is required for normal vegetative growth and genome stability. In such cases, conditional loss-of-function mutants can be useful...
2018: Methods in Enzymology
Eleni P Mimitou, Scott Keeney
During meiosis, the specialized cell division giving rise to gametes, numerous DNA double-strand breaks (DSBs) are introduced at multiple places throughout the genome by the topoisomerase-like protein Spo11. Homologous recombination, a highly conserved DSB repair pathway, is employed for their repair and ensures the formation of chiasmata and the proper segregation of homologous chromosomes. In the initial steps of recombination, end resection takes place, wherein Spo11 is endonucleolytically released and the 5'-terminal strands of each DSB are exonucleolytically processed, exposing the ssDNA necessary to identify a homologous repair template...
2018: Methods in Enzymology
Shannon Owens, Shangming Tang, Neil Hunter
Homologous recombination is fundamental to sexual reproduction, facilitating accurate segregation of homologous chromosomes at the first division of meiosis, and creating novel allele combinations that fuel evolution. Following initiation of meiotic recombination by programmed DNA double-strand breaks (DSBs), homologous pairing and DNA strand exchange form joint molecule (JM) intermediates that are ultimately resolved into crossover and noncrossover repair products. Physical monitoring of the DNA steps of meiotic recombination in Saccharomyces cerevisiae (budding yeast) cultures undergoing synchronous meiosis has provided seminal insights into the molecular basis of meiotic recombination and affords a powerful tool for dissecting the molecular roles of recombination factors...
2018: Methods in Enzymology
Davide Moiani, Daryl A Ronato, Chris A Brosey, Andrew S Arvai, Aleem Syed, Jean-Yves Masson, Elena Petricci, John A Tainer
For inhibitor design, as in most research, the best system is question dependent. We suggest structurally defined allostery to design specific inhibitors that target regions beyond active sites. We choose systems allowing efficient quality structures with conformational changes as optimal for structure-based design to optimize inhibitors. We maintain that evolutionarily related targets logically provide molecular avatars, where this Sanskrit term for descent includes ideas of functional relationships and of being a physical embodiment of the target's essential features without requiring high sequence identity...
2018: Methods in Enzymology
Liangyu Zhang, Simone Köhler, Regina Rillo-Bohn, Abby F Dernburg
During meiosis, each pair of homologous chromosomes typically undergoes at least one crossover (crossover assurance), but these exchanges are strictly limited in number and widely spaced along chromosomes (crossover interference). The molecular basis for this chromosome-wide regulation remains mysterious. A family of meiotic RING finger proteins has been implicated in crossover regulation across eukaryotes. Caenorhabditis elegans expresses four such proteins, of which one (ZHP-3) is known to be required for crossovers...
March 9, 2018: ELife
Shun Bai, Le Cheng, Yingwen Zhang, Chunsen Zhu, Zhiping Zhu, Ruping Zhu, C Yan Cheng, Lan Ye, Ke Zheng
STUDY QUESTION: What is the physiological role of Rictor in spermatogenic cells? SUMMARY ANSWER: Germline expression of Rictor regulates spermatogonial differentiation and has an essential role in coordinating germ cells and Sertoli cells in maintaining intact cell-cell adhesion dynamics and cytoskeleton-based architecture in the seminiferous epithelium. WHAT IS KNOWN ALREADY: The mechanistic target of rapamycin (mTOR) resides in its functions as the catalytic subunits of the structurally and functionally distinct mTORC1 and mTORC2 complexes...
February 6, 2018: Molecular Human Reproduction
Ifeyinwa Onyemaobi, Habtamu Ayalew, Hui Liu, Kadambot H M Siddique, Guijun Yan
Grain number is a major trait for wheat yield under dryland farming. An International Triticeae Mapping Initiative (ITMI) mapping population comprising 105 recombinant inbred lines (RIL) developed from a cross between a Synthetic hexaploid wheat (Triticum aestivum) 'W7984' and a spring wheat variety 'Opata M85' was used to identify quantitative trait loci (QTL) associated with grain number per spike under two treatment conditions, normal watering and water stress during meiosis. Two major QTL for grain number per spike on the main stem Q...
2018: PloS One
Rhea Kang, Maciej J Zelazowski, Francesca Cole
PRDM9 determines the localization of meiotic recombination hotspots, which are associated with histone H3 methylation. It is not known whether PRDM9's methyltransferase activity is required or how some PRDM9 alleles can dominate the distribution of hotspots over other alleles. Diagouraga, Clément, and colleagues (2018) show that methyltransferase activity is required for hotspot localization and that this activity is additive in combination, suggesting that the dominance of particular alleles is simply proportional to the frequency of targeted sites...
March 1, 2018: Molecular Cell
Andrew Lloyd, Chris Morgan, Chris Franklin, Kirsten Bomblies
Meiotic recombination shuffles genetic information from sexual species into gametes to create novel combinations in offspring. Thus, recombination is an important factor in inheritance, adaptation and responses to selection. However, recombination is not a static parameter - meiotic recombination rate is sensitive to variation in the environment, especially temperature. That recombination rates change in response to both increases and decreases in temperature was reported in Drosophila a century ago, and since then in several other species...
March 1, 2018: Genetics
Yingxiang Wang, Gregory P Copenhaver
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...
February 28, 2018: Annual Review of Plant Biology
Stacie E Hughes, Danny E Miller, Angela L Miller, R Scott Hawley
A century of genetic studies of the meiotic process in Drosophila melanogaster females has been greatly augmented by both modern molecular biology and major advances in cytology. These approaches, and the findings they have allowed, are the subject of this review. Specifically, these efforts have revealed that meiotic pairing in Drosophila females is not an extension of somatic pairing, but rather occurs by a poorly understood process during premeiotic mitoses. This process of meiotic pairing requires the function of several components of the synaptonemal complex (SC)...
March 2018: Genetics
Nuria Ferrandiz, Consuelo Barroso, Oana Telecan, Nan Shao, Hyun-Min Kim, Sarah Testori, Peter Faull, Pedro Cutillas, Ambrosious P Snijders, Monica P Colaiácovo, Enrique Martinez-Perez
The formation of haploid gametes from diploid germ cells requires the regulated two-step release of sister chromatid cohesion (SCC) during the meiotic divisions. Here, we show that phosphorylation of cohesin subunit REC-8 by Aurora B promotes SCC release at anaphase I onset in C. elegans oocytes. Aurora B loading to chromatin displaying Haspin-mediated H3 T3 phosphorylation induces spatially restricted REC-8 phosphorylation, preventing full SCC release during anaphase I. H3 T3 phosphorylation is locally antagonized by protein phosphatase 1, which is recruited to chromosomes by HTP-1/2 and LAB-1...
February 26, 2018: Nature Communications
Rachel Reichman, Zhuoyue Shi, Robert Malone, Sarit Smolikove
Meiosis is a highly regulated process, partly due to the need to break and then repair DNA as part of the meiotic program. Post-translational modifications are widely used during meiotic events to regulate steps such as protein complex formation, checkpoint activation, and protein attenuation. In this paper, we investigate how proteins that are obligatory components of the SUMO pathway, one such post-translational modification, affect the C. elegans germline. We show that UBC-9, the E2 conjugation enzyme, and the C...
February 22, 2018: Genetics
Heïdi Serra, Christophe Lambing, Catherine H Griffin, Stephanie D Topp, Divyashree C Nageswaran, Charles J Underwood, Piotr A Ziolkowski, Mathilde Séguéla-Arnaud, Joiselle B Fernandes, Raphaël Mercier, Ian R Henderson
During meiosis, homologous chromosomes undergo reciprocal crossovers, which generate genetic diversity and underpin classical crop improvement. Meiotic recombination initiates from DNA double-strand breaks (DSBs), which are processed into single-stranded DNA that can invade a homologous chromosome. The resulting joint molecules can ultimately be resolved as crossovers. In Arabidopsis , competing pathways balance the repair of ∼100-200 meiotic DSBs into ∼10 crossovers per meiosis, with the excess DSBs repaired as noncrossovers...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
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