scholarly journals Meiotic Crossover Patterning

2021 ◽  
Vol 9 ◽  
Author(s):  
Nila M. Pazhayam ◽  
Carolyn A. Turcotte ◽  
Jeff Sekelsky
Keyword(s):  
Chromosome Segregation ◽  
Chromosome Pair ◽  
Double Strand Breaks ◽  
Current Understanding ◽  
Genetic Studies ◽  
Strand Breaks ◽  
Proper Number ◽  
Key Players ◽  
Meiotic Crossover ◽  
History Of

Proper number and placement of meiotic crossovers is vital to chromosome segregation, with failures in normal crossover distribution often resulting in aneuploidy and infertility. Meiotic crossovers are formed via homologous repair of programmed double-strand breaks (DSBs). Although DSBs occur throughout the genome, crossover placement is intricately patterned, as observed first in early genetic studies by Muller and Sturtevant. Three types of patterning events have been identified. Interference, first described by Sturtevant in 1915, is a phenomenon in which crossovers on the same chromosome do not occur near one another. Assurance, initially identified by Owen in 1949, describes the phenomenon in which a minimum of one crossover is formed per chromosome pair. Suppression, first observed by Beadle in 1932, dictates that crossovers do not occur in regions surrounding the centromere and telomeres. The mechanisms behind crossover patterning remain largely unknown, and key players appear to act at all scales, from the DNA level to inter-chromosome interactions. There is also considerable overlap between the known players that drive each patterning phenomenon. In this review we discuss the history of studies of crossover patterning, developments in methods used in the field, and our current understanding of the interplay between patterning phenomena.

scholarly journals Mammalian CNTD1 is critical for meiotic crossover maturation and deselection of excess precrossover sites

2014 ◽  
Vol 205 (5) ◽  
pp. 633-641 ◽  
Author(s):  
J. Kim Holloway ◽  
Xianfei Sun ◽  
Rayka Yokoo ◽  
Anne M. Villeneuve ◽  
Paula E. Cohen
Keyword(s):  
Chromosome Segregation ◽  
Meiotic Recombination ◽  
Homologous Chromosome ◽  
Ring Finger ◽  
Double Strand Breaks ◽  
Related Protein ◽  
Strand Breaks ◽  
Meiotic Crossover ◽  
Specific Factors ◽  
Ring Finger Proteins

Meiotic crossovers (COs) are crucial for ensuring accurate homologous chromosome segregation during meiosis I. Because the double-strand breaks (DSBs) that initiate meiotic recombination greatly outnumber eventual COs, this process requires exquisite regulation to narrow down the pool of DSB intermediates that may form COs. In this paper, we identify a cyclin-related protein, CNTD1, as a critical mediator of this process. Disruption of Cntd1 results in failure to localize CO-specific factors MutLγ and HEI10 at designated CO sites and also leads to prolonged high levels of pre-CO intermediates marked by MutSγ and RNF212. These data show that maturation of COs is intimately coupled to deselection of excess pre-CO sites to yield a limited number of COs and that CNTD1 coordinates these processes by regulating the association between the RING finger proteins HEI10 and RNF212 and components of the CO machinery.

scholarly journals Recombination patterns in maize reveal limits to crossover homeostasis

2015 ◽  
Vol 112 (52) ◽  
pp. 15982-15987 ◽  
Author(s):  
Gaganpreet K. Sidhu ◽  
Celestia Fang ◽  
Mischa A. Olson ◽  
Matthieu Falque ◽  
Olivier C. Martin ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Chromosome Segregation ◽  
Meiotic Recombination ◽  
Chromosome Pair ◽  
Double Strand Breaks ◽  
Chromosomal Dna ◽  
Strand Breaks ◽  
Homologous Chromosomes ◽  
Physiological Conditions ◽  
Transgenic Lines

During meiotic recombination, double-strand breaks (DSBs) are formed in chromosomal DNA and then repaired as either crossovers (COs) or non–crossovers (NCOs). In most taxa, the number of DSBs vastly exceeds the number of COs. COs are required for generating genetic diversity in the progeny, as well as proper chromosome segregation. Their formation is tightly controlled so that there is at least one CO per pair of homologous chromosomes whereas the maximum number of COs per chromosome pair is fairly limited. One of the main mechanisms controlling the number of recombination events per meiosis is CO homeostasis, which maintains a stable CO number even when the DSB number is dramatically altered. The existence of CO homeostasis has been reported in several species, including mouse, yeast, and Caenorhabditis elegans. However, it is not known whether homeostasis exists in the same form in all species. In addition, the studies of homeostasis have been conducted using mutants and/or transgenic lines exhibiting fairly severe meiotic phenotypes, and it is unclear how important homeostasis is under normal physiological conditions. We found that, in maize, CO control is robust only to ensure one CO per chromosome pair. However, once this limit is reached, the CO number is linearly related to the DSB number. We propose that CO control is a multifaceted process whose different aspects have a varying degree of importance in different species.

scholarly journals FIGL1 and its novel partner FLIP form a conserved complex that regulates homologous recombination

2017 ◽  
Author(s):  
Joiselle Blanche Fernandes ◽  
Marine Duhamel ◽  
Mathilde Séguéla-Arnaud ◽  
Nicole Froger ◽  
Chloé Girard ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Chromosome Segregation ◽  
Double Strand Breaks ◽  
Genetic Screens ◽  
Dna Double Strand Breaks ◽  
Interacting Protein ◽  
Strand Breaks ◽  
Protein Protein Interaction ◽  
Meiotic Crossover ◽  
Strand Invasion

AbstractHomologous recombination is central to repair DNA double-strand breaks (DSB), either accidently arising in mitotic cells or in a programed manner at meiosis. Crossovers resulting from the repair of meiotic breaks are essential for proper chromosome segregation and increase genetic diversity of the progeny. However, mechanisms regulating CO formation remain elusive. Here, we identified through protein-protein interaction and genetic screens FIDGETIN-LIKE-1 INTERACTING PROTEIN (FLIP) as a new partner of the previously characterized anti-crossover factor FIDGETIN-LIKE-1 (FIGL1) in Arabidopsis thaliana. We showed that FLIP limits meiotic crossover together with FIGL1. Further, FLIP and FIGL1 form a protein complex conserved from Arabidopsis to Human. FIGL1 interacts with the recombinases RAD51 and DMC1, the enzymes that catalyze the DNA stand exchange step of homologous recombination. Arabidopsis flip mutants recapitulates the figl1 phenotype, with enhanced meiotic recombination associated with change in DMC1 dynamics. Our data thus suggest that FLIP and FIGL1 form a conserved complex that regulates the crucial step of strand invasion in homologous recombination.

scholarly journals Estimation of Rearrangement Break Rates Across the Genome

2018 ◽  
Author(s):  
Christopher Hann-Soden ◽  
Ian Holmes ◽  
John W. Taylor
Keyword(s):  
Neurospora Crassa ◽  
Interval Graph ◽  
Double Strand Breaks ◽  
Genomic Rearrangements ◽  
Strand Breaks ◽  
Minimum Cover ◽  
A Genome ◽  
History Of ◽  
Cover Problem ◽  
Special Case

Genomic rearrangements provide an important source of variation, but reconstructing the history of rearrangements often has many solutions. We answer the question of where rearrangements occur by solving the simpler problem of estimating the rate of double-strand breaks at every site in a genome. This problem is a special case of the minimum cover problem for an interval graph. We implement this method as a Python program, BRAG, and use it to estimate break rates in the genome of Neurospora crassa. We find that more frequent rearrangement in the subtelomeres facilitates the evolution of novel genes.

scholarly journals Persistent DNA Repair Signaling and DNA Polymerase Theta Promote Broken Chromosome Segregation

2021 ◽  
Author(s):  
Delisa E Clay ◽  
Heidi S Bretscher ◽  
Erin Jezuit ◽  
Korie Bush ◽  
Donald T Fox
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Dna Polymerase ◽  
Chromosome Segregation ◽  
Genome Instability ◽  
Double Strand Breaks ◽  
End Joining ◽  
Strand Breaks ◽  
Alternative End Joining ◽  
Segregation Of Chromosomes

Cycling cells must respond to double-strand breaks (DSBs) to avoid genome instability. Mis-segregation of chromosomes with DSBs during mitosis results in micronuclei, aberrant structures linked to disease. How cells respond to DSBs during mitosis is incompletely understood. We previously showed that Drosophila papillar cells lack DSB checkpoints (as observed in many cancer cells). Here, we show that papillar cells still recruit early-acting repair machinery (Mre11 and RPA3) to DSBs. This machinery persists as foci on DSBs as cells enter mitosis. Repair foci are resolved in a step-wise manner during mitosis. Repair signaling kinetics at DSBs depends on both monoubiquitination of the Fanconi Anemia (FA) protein Fancd2 and the alternative end- joining protein DNA Polymerase Theta. Disruption of either or both of these factors causes micronuclei after DNA damage, which disrupts intestinal organogenesis. This study reveals a mechanism for how cells with inactive DSB checkpoints can respond to DNA damage that persists into mitosis.

scholarly journals Activation of meiotic recombination by nuclear import of the DNA break hotspot-determining complex in fission yeast

2021 ◽  
Vol 134 (4) ◽  
pp. jcs253518 ◽  
Author(s):  
Mélody Wintrebert ◽  
Mai-Chi Nguyen ◽  
Gerald R. Smith
Keyword(s):  
Chromosome Segregation ◽  
Meiotic Recombination ◽  
High Specificity ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Nuclear Entry ◽  
Strand Breaks ◽  
Protein Complex Formation ◽  
Complex Process ◽  
Localization Signal

ABSTRACTMeiotic recombination forms crossovers important for proper chromosome segregation and offspring viability. This complex process involves many proteins acting at each of the multiple steps of recombination. Recombination initiates by formation of DNA double-strand breaks (DSBs), which in the several species examined occur with high frequency at special sites (DSB hotspots). In Schizosaccharomyces pombe, DSB hotspots are bound with high specificity and strongly activated by linear element (LinE) proteins Rec25, Rec27 and Mug20, which form colocalized nuclear foci with Rec10, essential for all DSB formation and recombination. Here, we test the hypothesis that the nuclear localization signal (NLS) of Rec10 is crucial for coordinated nuclear entry after forming a complex with other LinE proteins. In NLS mutants, all LinE proteins were abundant in the cytoplasm, not the nucleus; DSB formation and recombination were much reduced but not eliminated. Nuclear entry of limited amounts of Rec10, apparently small enough for passive nuclear entry, can account for residual recombination. LinE proteins are related to synaptonemal complex proteins of other species, suggesting that they also share an NLS, not yet identified, and undergo protein complex formation before nuclear entry.This article has an associated First Person interview with Mélody Wintrebert, joint first author of the paper.

scholarly journals ATR/Mec1 prevents lethal meiotic recombination initiation on partially replicated chromosomes in budding yeast

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Hannah G Blitzblau ◽  
Andreas Hochwagen
Keyword(s):  
Chromosome Segregation ◽  
Budding Yeast ◽  
Meiotic Chromosome ◽  
Double Strand Breaks ◽  
Genome Integrity ◽  
Dna Double Strand Breaks ◽  
Rapid Loss ◽  
Replication Checkpoint ◽  
Strand Breaks ◽  
Cdc7 Kinase

During gamete formation, crossover recombination must occur on replicated DNA to ensure proper chromosome segregation in the first meiotic division. We identified a Mec1/ATR- and Dbf4-dependent replication checkpoint in budding yeast that prevents the earliest stage of recombination, the programmed induction of DNA double-strand breaks (DSBs), when pre-meiotic DNA replication was delayed. The checkpoint acts through three complementary mechanisms: inhibition of Mer2 phosphorylation by Dbf4-dependent Cdc7 kinase, preclusion of chromosomal loading of Rec114 and Mre11, and lowered abundance of the Spo11 nuclease. Without this checkpoint, cells formed DSBs on partially replicated chromosomes. Importantly, such DSBs frequently failed to be repaired and impeded further DNA synthesis, leading to a rapid loss in cell viability. We conclude that a checkpoint-dependent constraint of DSB formation to duplicated DNA is critical not only for meiotic chromosome assortment, but also to protect genome integrity during gametogenesis.

scholarly journals Mechanism of in vivo activation of the MutLγ-Exo1 complex for meiotic crossover formation

2019 ◽  
Author(s):  
Aurore Sanchez ◽  
Céline Adam ◽  
Felix Rauh ◽  
Yann Duroc ◽  
Lepakshi Ranjha ◽  
...  
Keyword(s):  
Direct Interaction ◽  
Double Strand Breaks ◽  
Repair Pathway ◽  
Spatial Control ◽  
Strand Breaks ◽  
Catalytic Function ◽  
Polo Kinase ◽  
Meiotic Crossover ◽  
Temporal And Spatial

AbstractCrossovers generated during the repair of programmed double-strand breaks (DSBs) during homologous recombination are essential for fertility to allow accurate homolog segregation during the first meiotic division. Most crossovers arise through the cleavage of recombination intermediates by the Mlh1-Mlh3 (MutLγ) endonuclease and an elusive non-catalytic function of Exo1, and require the Polo kinase Cdc5. Here we show in budding yeast that MutLγ forms a constitutive complex with Exo1, and in meiotic cells transiently contacts the Msh4-Msh5 (MutSγ) heterodimer, also required for crossover formation. We further show that MutLγ-Exo1 associates with recombination intermediates once they are committed to the crossover repair pathway, and then Exo1 recruits Cdc5 through a direct interaction that is required for activating MutLγ and crossover formation. Exo1 therefore serves as a non-catalytic matchmaker between Cdc5 and MutLγ. We finally show that in vivo, MutLγ associates with the vast majority of DSB hotspots, but at a lower frequency near centromeres, consistent with a strategy to reduce at-risk crossover events in these regions. Our data highlight the tight temporal and spatial control of the activity of a constitutive, potentially harmful, nuclease.

scholarly journals CRISPR targeting of MEIOTIC-TOPOISOMERASE VIB-dCas9 to a recombination hotspot is insufficient to increase crossover frequency in Arabidopsis

2021 ◽  
Author(s):  
Nataliya E. Yelina ◽  
Sabrina Gonzalez-Jorge ◽  
Dominique Hirsz ◽  
Ziyi Yang ◽  
Ian R. Henderson
Keyword(s):  
Meiotic Recombination ◽  
Crop Improvement ◽  
Double Strand Breaks ◽  
Crossover Frequency ◽  
Dna Double Strand Breaks ◽  
Crop Breeding ◽  
Catalytic Subunits ◽  
Strand Breaks ◽  
Homologous Chromosomes ◽  
Meiotic Crossover

AbstractDuring meiosis, homologous chromosomes pair and recombine, which can result in reciprocal crossovers that increase genetic diversity. Crossovers are unevenly distributed along eukaryote chromosomes and show repression in heterochromatin and the centromeres. Within the chromosome arms crossovers are often concentrated in hotspots, which are typically in the kilobase range. The uneven distribution of crossovers along chromosomes, together with their low number per meiosis, creates a limitation during crop breeding, where recombination can be beneficial. Therefore, targeting crossovers to specific genome locations has the potential to accelerate crop improvement. In plants, meiotic crossovers are initiated by DNA double strand breaks (DSBs) that are catalysed by SPO11 complexes, which consist of two catalytic (SPO11-1 and SPO11-2) and two non-catalytic subunits (MTOPVIB). We used the model plant Arabidopsis thaliana to target a dCas9-MTOPVIB fusion protein to the 3a crossover hotspot via CRISPR. We observed that this was insufficient to significantly change meiotic crossover frequency or pattern within 3a. We discuss the implications of our findings for targeting meiotic recombination within plant genomes.

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