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Meiotic recombination

Philippe Lefrançois, Beth Rockmill, Pingxing Xie, G Shirleen Roeder, Michael Snyder
During meiosis, chromosomes undergo a homology search in order to locate their homolog to form stable pairs and exchange genetic material. Early in prophase, chromosomes associate in mostly non-homologous pairs, tethered only at their centromeres. This phenomenon, conserved through higher eukaryotes, is termed centromere coupling in budding yeast. Both initiation of recombination and the presence of homologs are dispensable for centromere coupling (occurring in spo11 mutants and haploids induced to undergo meiosis) but the presence of the synaptonemal complex (SC) protein Zip1 is required...
October 2016: PLoS Genetics
Friederike Finsterbusch, Ramya Ravindranathan, Ihsan Dereli, Marcello Stanzione, Daniel Tränkner, Attila Tóth
Orderly chromosome segregation during the first meiotic division requires meiotic recombination to form crossovers between homologous chromosomes (homologues). Members of the minichromosome maintenance (MCM) helicase family have been implicated in meiotic recombination. In addition, they have roles in initiation of DNA replication, DNA mismatch repair and mitotic DNA double-strand break repair. Here, we addressed the function of MCMDC2, an atypical yet conserved MCM protein, whose function in vertebrates has not been reported...
October 2016: PLoS Genetics
Julian Lange, Shintaro Yamada, Sam E Tischfield, Jing Pan, Seoyoung Kim, Xuan Zhu, Nicholas D Socci, Maria Jasin, Scott Keeney
Heritability and genome stability are shaped by meiotic recombination, which is initiated via hundreds of DNA double-strand breaks (DSBs). The distribution of DSBs throughout the genome is not random, but mechanisms molding this landscape remain poorly understood. Here, we exploit genome-wide maps of mouse DSBs at unprecedented nucleotide resolution to uncover previously invisible spatial features of recombination. At fine scale, we reveal a stereotyped hotspot structure-DSBs occur within narrow zones between methylated nucleosomes-and identify relationships between SPO11, chromatin, and the histone methyltransferase PRDM9...
October 20, 2016: Cell
Sonika Ahlawat, Sachinandan De, Priyanka Sharma, Rekha Sharma, Reena Arora, R S Kataria, T K Datta, R K Singh
Hybrid sterility or reproductive isolation in mammals has been attributed to allelic incompatibilities in a DNA-binding protein PRDM9. Not only is PRDM9 exceptional in being the only known 'speciation gene' in vertebrates, but it is also considered to be the fastest evolving gene in the genome. The terminal zinc finger (ZF) domain of PRDM9 specifies genome-wide meiotic recombination hotspot locations in mammals. Intriguingly, PRDM9 ZF domain is highly variable between as well as within species, possibly activating different recombination hotspots...
October 15, 2016: Molecular Genetics and Genomics: MGG
Ferdouse Begum, Reshmi Chowdhury, Vivian Cheung, Stephanie Sherman, Eleanor Feingold
Meiotic recombination is an essential step in gametogenesis and is one that also generates genetic diversity. Genome-wide association and molecular studies have identified genes that influence of human meiotic recombination. RNF212 is associated with total or average number of recombination events, and PRDM9 is associated with the locations of hotspots, or sequences where crossing over appears to cluster. In addition, a common inversion on chromosome 17 is strongly associated with recombination. Other genes have been identified by GWAS, but those results have not been replicated...
October 12, 2016: G3: Genes—Genomes—Genetics
Marcello Stanzione, Marek Baumann, Frantzeskos Papanikos, Ihsan Dereli, Julian Lange, Angelique Ramlal, Daniel Tränkner, Hiroki Shibuya, Bernard de Massy, Yoshinori Watanabe, Maria Jasin, Scott Keeney, Attila Tóth
DNA double-strand breaks (DSBs) are induced by SPO11 during meiosis to initiate recombination-mediated pairing and synapsis of homologous chromosomes. Germline genome integrity requires spatiotemporal control of DSB formation, which involves the proteinaceous chromosome axis along the core of each meiotic chromosome. In particular, a component of unsynapsed axes, HORMAD1, promotes DSB formation in unsynapsed regions where DSB formation must occur to ensure completion of synapsis. Despite its importance, the underlying mechanism has remained elusive...
October 10, 2016: Nature Cell Biology
Tyler S Machovina, Rana Mainpal, Anahita Daryabeigi, Olivia McGovern, Dimitra Paouneskou, Sara Labella, Monique Zetka, Verena Jantsch, Judith L Yanowitz
Crossover (CO) recombination creates a physical connection between homologs that promotes their proper segregation at meiosis I (MI). Failure to realize an obligate CO causes homologs to attach independently to the MI spindle and separate randomly, leading to nondisjunction. However, mechanisms that determine whether homolog pairs have received crossovers remain mysterious. Here we describe a surveillance system in C. elegans that monitors recombination intermediates and couples their formation to meiotic progression...
October 1, 2016: Current Biology: CB
Anitha Sundararajan, Stefanie Dukowic-Schulze, Madeline Kwicklis, Kayla Engstrom, Nathan Garcia, Oliver J Oviedo, Thiruvarangan Ramaraj, Michael D Gonzales, Yan He, Minghui Wang, Qi Sun, Jaroslaw Pillardy, Shahryar F Kianian, Wojciech P Pawlowski, Changbin Chen, Joann Mudge
Recombination occurring during meiosis is critical for creating genetic variation and plays an essential role in plant evolution. In addition to creating novel gene combinations, recombination can affect genome structure through altering GC patterns. In maize (Zea mays) and other grasses, another intriguing GC pattern exists. Maize genes show a bimodal GC content distribution that has been attributed to nucleotide bias in the third, or wobble, position of the codon. Recombination may be an underlying driving force given that recombination sites are often associated with high GC content...
2016: Frontiers in Plant Science
Arun Kanakkanthara, Karthik B Jeganathan, Jazeel F Limzerwala, Darren J Baker, Masakazu Hamada, Hyun-Ja Nam, Willemijn H van Deursen, Naomi Hamada, Ryan M Naylor, Nicole A Becker, Brian A Davies, Janine H van Ree, Georges Mer, Virginia S Shapiro, L James Maher, David J Katzmann, Jan M van Deursen
Cyclin A2 activates the cyclin-dependent kinases Cdk1 and Cdk2 and is expressed at elevated levels from S phase until early mitosis. We found that mutant mice that cannot elevate cyclin A2 are chromosomally unstable and tumor-prone. Underlying the chromosomal instability is a failure to up-regulate the meiotic recombination 11 (Mre11) nuclease in S phase, which leads to impaired resolution of stalled replication forks, insufficient repair of double-stranded DNA breaks, and improper segregation of sister chromosomes...
September 30, 2016: Science
Aimee Jaramillo-Lambert, Amy S Fabritius, Tyler J Hansen, Harold E Smith, Andy Golden
Topoisomerase II alleviates DNA entanglements that are generated during mitotic DNA replication, transcription, and sister chromatid separation. In contrast to mitosis, meiosis has two rounds of chromosome segregation following one round of DNA replication. In meiosis II, sister chromatids segregate from each other similar to mitosis. Meiosis I, on the other hand, segregates homologs, which requires pairing, synapsis, and recombination. The exact role that topoisomerase II plays during meiosis is unknown. In a screen re-examining Caenorhabditis elegant legacy mutants isolated thirty years ago, we identified a novel allele of the gene encoding topoisomerase II, top-2(it7) In this study, we demonstrate that top-2(it7) males produce dead embryos, even when fertilizing wild-type oocytes...
October 5, 2016: Genetics
Elissa J Chesler, Daniel M Gatti, Andrew P Morgan, Marge Strobel, Laura Trepanier, Denesa Oberbeck, Shannon McWeeney, Robert Hitzemann, Martin Ferris, Rachel McMullan, Amelia Clayshultle, Timothy A Bell, Fernando Pardo-Manuel de Villena, Gary A Churchill
Multi-parent populations (MPPs) capture and maintain the genetic diversity from multiple inbred founder strains to provide a resource for high-resolution genetic mapping through the accumulation of recombination events over many generations. Breeding designs that maintain a large effective population size with randomized assignment of breeders at each generation can minimize the impact of selection, inbreeding, and genetic drift on allele frequencies. Small deviations from expected allele frequencies will have little effect on the power and precision of genetic analysis, but a major distortion could result in reduced power and loss of important functional alleles...
September 30, 2016: G3: Genes—Genomes—Genetics
T Brooke McClendon, Rana Mainpal, Francis Raj Gandhi Amrit, Michael W Krause, Arjumand Ghazi, Judith L Yanowitz
The germ line efficiently combats numerous genotoxic insults to ensure the high fidelity propagation of unaltered genomic information across generations. Yet, germ cells in most metazoans also intentionally create double-strand breaks (DSBs) to promote DNA exchange between parental chromosomes, a process known as crossing over. Homologous recombination is employed in the repair of both genotoxic lesions and programmed DSBs and many of the core DNA repair proteins function in both processes. In addition, DNA repair efficiency and crossover distribution are both influenced by local and global differences in chromatin structure, yet the interplay between chromatin structure, genome integrity, and meiotic fidelity is still poorly understand...
October 5, 2016: G3: Genes—Genomes—Genetics
Nicole A Najor, Layne Weatherford, George S Brush
In the budding yeast Saccharomyces cerevisiae, unnatural stabilization of the cyclin-dependent kinase inhibitor Sic1 during meiosis can trigger extra rounds of DNA replication. When programmed DNA double-strand breaks are generated but not repaired due to absence of DMC1, a pathway involving the checkpoint gene RAD17 prevents this DNA rereplication. Further genetic analysis has now revealed that prevention of DNA rereplication also requires MEC1, which encodes a protein kinase that serves as a central checkpoint regulator in several pathways including the meiotic recombination checkpoint response...
September 27, 2016: G3: Genes—Genomes—Genetics
Kyeoung-Hwa Kim, Ji-Hoon Park, Eun-Young Kim, Jung-Jae Ko, Kyung-Soon Park, Kyung-Ah Lee
Rad51 is a conserved eukaryotic protein that mediates the homologous recombination repair of DNA double-strand breaks that occur during mitosis and meiosis. In addition, Rad51 promotes mitochondrial DNA synthesis when replication stress is increased. Rad51 also regulates cell cycle progression by preserving the G2/M transition in embryonic stem cells. In this study, we report a novel function of Rad51 in regulating mitochondrial activity during in vitro maturation of mouse oocytes. Suppression of Rad51 by injection of Rad51 dsRNA into germinal vesicle-stage oocytes resulted in arrest of meiosis in metaphase I...
September 28, 2016: Scientific Reports
Mei Rong, Atsushi Matsuda, Yasushi Hiraoka, Jibak Lee
Cohesins containing a meiosis-specific α-kleisin subunit, RAD21L or REC8, play roles in diverse aspects of meiotic chromosome dynamics including formation of axial elements (AEs), assembly of the synaptonemal complex (SC), recombination of homologous chromosomes, and cohesion of sister chromatids. However, the exact functions of individual α-kleisins remain to be elucidated. Here, we examined the localization of RAD21L and REC8 within the SC by super-resolution microscopy, 3D-SIM. We found that both RAD21L and REC8 were localized at the connection sites between lateral elements (LEs) and transverse filaments (TFs) of pachynema with RAD21L locating interior to REC8 sites...
September 26, 2016: Journal of Reproduction and Development
Xuli Zhu, Huan Li, Meixia Ye, Libo Jiang, Mengmeng Sang, Rongling Wu
Allopolyploids are a group of polyploids with more than two sets of chromosomes derived from different species. Previous linkage analysis of allopolyploids is based on the assumption that different chromosomes pair randomly during meiosis. A more sophisticated model to relax this assumption has been developed for allotetraploids by incorporating the preferential pairing behavior of homologous over homoeologous chromosomes. Here, we show that the basic principle of this model can be extended to perform linkage analysis of higher-ploidy allohexaploids, where multiple preferential pairing factors are used to characterize chromosomal-pairing meiotic features between different constituent species...
September 19, 2016: Briefings in Bioinformatics
Stephen Gray, Paula E Cohen
Meiosis, the mechanism of creating haploid gametes, is a complex cellular process observed across sexually reproducing organisms. Fundamental to meiosis is the process of homologous recombination, whereby DNA double-strand breaks are introduced into the genome and are subsequently repaired to generate either noncrossovers or crossovers. Although homologous recombination is essential for chromosome pairing during prophase I, the resulting crossovers are critical for maintaining homolog interactions and enabling accurate segregation at the first meiotic division...
September 14, 2016: Annual Review of Genetics
David Porubsky, Ashley D Sanders, Niek van Wietmarschen, Ester Falconer, Mark Hills, Diana C J Spierings, Marianna R Bevova, Victor Guryev, Peter Michael Lansdorp
Haplotypes are fundamental to fully characterize the diploid genome of an individual, yet methods to directly chart the unique genetic makeup of each parental chromosome are lacking. Here we introduce single cell DNA template strand sequencing (Strand-seq) as a novel approach to phasing diploid genomes along the entire length of all chromosomes. We demonstrate this by building a complete haplotype for HapMap individual (NA12878) at high accuracy (concordance 99.3%), without using generational information or statistical inference...
September 19, 2016: Genome Research
Tiago Ribeiro, André Marques, Petr Novák, Veit Schubert, André L L Vanzela, Jiri Macas, Andreas Houben, Andrea Pedrosa-Harand
Satellite DNA repeats (or satDNA) are fast-evolving sequences usually associated with condensed heterochromatin. To test whether the chromosomal organisation of centromeric and non-centromeric satDNA differs in species with holocentric chromosomes, we identified and characterised the major satDNA families in the holocentric Cyperaceae species Rhynchospora ciliata (2n = 10), R. globosa (2n = 50) and R. tenuis (2n = 2x = 4 and 2n = 4x = 8). While conserved centromeric repeats (present in R. ciliata and R...
September 19, 2016: Chromosoma
Bjarni V Halldorsson, Marteinn T Hardarson, Birte Kehr, Unnur Styrkarsdottir, Arnaldur Gylfason, Gudmar Thorleifsson, Florian Zink, Adalbjorg Jonasdottir, Aslaug Jonasdottir, Patrick Sulem, Gisli Masson, Unnur Thorsteinsdottir, Agnar Helgason, Augustine Kong, Daniel F Gudbjartsson, Kari Stefansson
Meiotic recombination involves a combination of gene conversion and crossover events that, along with mutations, produce germline genetic diversity. Here we report the discovery of 3,176 SNP and 61 indel gene conversions. Our estimate of the non-crossover (NCO) gene conversion rate (G) is 7.0 for SNPs and 5.8 for indels per megabase per generation, and the GC bias is 67.6%. For indels, we demonstrate a 65.6% preference for the shorter allele. NCO gene conversions from mothers are longer than those from fathers, and G is 2...
September 19, 2016: Nature Genetics
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