scholarly journals DNA sequence differences are determinants of meiotic recombination outcome

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Simon D. Brown ◽  
Samantha J. Mpaulo ◽  
Mimi N. Asogwa ◽  
Marie Jézéquel ◽  
Matthew C. Whitby ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Relative Position ◽  
Meiotic Recombination ◽  
Strand Break ◽  
Intragenic Recombination ◽  
Strong Impact ◽  
Dna Helicases ◽  
Homologous Chromosomes ◽  
Dna Double Strand Break ◽  
Sequence Polymorphisms

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). 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.

scholarly journals DNA sequence differences are determinants of meiotic recombination outcome

2019 ◽  
Author(s):  
Simon D. Brown ◽  
Samantha J. Mpaulo ◽  
Mimi N. Asogwa ◽  
Marie Jézéquel ◽  
Matthew C. Whitby ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Relative Position ◽  
Meiotic Recombination ◽  
Strand Break ◽  
Intragenic Recombination ◽  
Strong Impact ◽  
Dna Helicases ◽  
Homologous Chromosomes ◽  
Dna Double Strand Break ◽  
Sequence Polymorphisms

AbstractMeiotic 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.PreambleDue to a mistake during analysis of a batch of Sanger sequencing reactions for Supplementary Figure S1, we erroneously stated that we found evidence for intragenic crossovers. We now show that intragenic crossovers are less likely than we initially thought. We sincerely apologize for our mishap and any inconvenience it might have caused. However, this does not affect the main conclusions of our paper, just how some of our results are interpreted. This new manuscript version has been amended accordingly.

scholarly journals Mouse TEX15 is essential for DNA double-strand break repair and chromosomal synapsis during male meiosis

2008 ◽  
Vol 180 (4) ◽  
pp. 673-679 ◽  
Author(s):  
Fang Yang ◽  
Sigrid Eckardt ◽  
N. Adrian Leu ◽  
K. John McLaughlin ◽  
Peijing Jeremy Wang
Keyword(s):  
Meiotic Recombination ◽  
Strand Break ◽  
Male Meiosis ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Homologous Chromosomes ◽  
Recombination Proteins ◽  
Meiotic Chromosomes ◽  
Dna Double Strand Break

During meiosis, homologous chromosomes undergo synapsis and recombination. We identify TEX15 as a novel protein that is required for chromosomal synapsis and meiotic recombination. Loss of TEX15 function in mice causes early meiotic arrest in males but not in females. Specifically, TEX15-deficient spermatocytes exhibit a failure in chromosomal synapsis. In mutant spermatocytes, DNA double-strand breaks (DSBs) are formed, but localization of the recombination proteins RAD51 and DMC1 to meiotic chromosomes is severely impaired. Based on these data, we propose that TEX15 regulates the loading of DNA repair proteins onto sites of DSBs and, thus, its absence causes a failure in meiotic recombination.

scholarly journals DNA helicases Sgs1 and BLM promote DNA double-strand break resection

2008 ◽  
Vol 22 (20) ◽  
pp. 2767-2772 ◽  
Author(s):  
S. Gravel ◽  
J. R. Chapman ◽  
C. Magill ◽  
S. P. Jackson
Keyword(s):  
Strand Break ◽  
Double Strand Break ◽  
Dna Helicases ◽  
Dna Double Strand Break

scholarly journals mus309 mutation, defective in DNA double-strand break repair, affects intergenic but not intragenic meiotic recombination in Drosophila melanogaster

2005 ◽  
Vol 86 (3) ◽  
pp. 185-191 ◽  
Author(s):  
PETTER PORTIN
Keyword(s):  
X Chromosome ◽  
Meiotic Recombination ◽  
Strand Break ◽  
Double Strand Break ◽  
Double Strand Break Repair ◽  
Crossing Over ◽  
Dna Double Strand Break ◽  
D Loop ◽  
Break Repair ◽  
Strand Annealing

The effect was investigated of the hypomorphic DNA double-strand break repair, notably synthesis-dependent strand annealing, deficient mutation mus309 on the third chromosome of Drosophila melanogaster on intergenic and intragenic meiotic recombination in the X chromosome. The results showed that the mutation significantly increases the frequency of intergenic crossing over in two of three gene intervals of the X chromosome studied. Interestingly the increase was most prevalent in the tip of the X chromosome where crossovers normally are least frequent per physical map unit length. In particular crossing over interference was also affected, indicating that the effect of the mus309 mutation involves preconditions of crossing over but not the event of crossing over itself. On the other hand, the results also show that most probably the mutation does not have any effect on intragenic recombination, i.e. gene conversion. These results are fully consistent with the present molecular models of meiotic crossing over initiated by double-strand breaks of DNA followed by formation of a single-end-invasion intermediate, or D-loop, which is subsequently processed to generate either crossover or non-crossover products involving formation of a double Holliday junction. In particular the results suggest that the mus309 gene is involved in resolution of the D-loop, thereby affecting the choice between double-strand-break repair (DSBR) and synthesis-dependent strand annealing (SDSA) pathways of meiotic recombination.

scholarly journals Mechanistic view and genetic control of DNA recombination during meiosis

2017 ◽  
Author(s):  
Marie-Claude Marsolier-Kergoat ◽  
Md Muntaz Khan ◽  
Jonathan Schott ◽  
Xuan Zhu ◽  
Bertrand Llorente
Keyword(s):  
Meiotic Recombination ◽  
Dna Recombination ◽  
Strand Break ◽  
Holliday Junctions ◽  
Switching Frequency ◽  
Template Switching ◽  
Genome Wide ◽  
Dna Double Strand Break ◽  
Strand Annealing ◽  
Mechanistic View

ABSTRACTMeiotic recombination is essential for fertility and allelic shuffling. Canonical recombination models fail to capture the observed complexity of meiotic recombinants. Here we revisit these models by analyzing meiotic heteroduplex DNA tracts genome-wide in combination with meiotic DNA double-strand break (DSB) locations. We provide unprecedented support to the synthesis-dependent strand annealing model and establish estimates of its associated template switching frequency and polymerase processivity. We show that resolution of double Holliday junctions (dHJs) is biased toward cleavage of the pair of strands containing newly synthesized DNA near the junctions. The suspected dHJ resolvase Mlh1-3 as well as Mlh1-2, Exo1 and Sgs1 promote asymmetric positioning of crossover intermediates relative to the initiating DSB and bidirectional conversions. Finally, we show that crossover-biased dHJ resolution depends on Mlh1-3, Exo1, Msh5 and to a lesser extent on Sgs1. These properties are likely conserved in eukaryotes containing the ZMM proteins, which includes mammals.

scholarly journals Sex without crossing over in the yeastSaccharomycodes ludwigii

2021 ◽  
Author(s):  
Ioannis A. Papaioannou ◽  
Fabien Dutreux ◽  
France A. Peltier ◽  
Hiromi Maekawa ◽  
Nicolas Delhomme ◽  
...  
Keyword(s):  
Meiotic Recombination ◽  
Strand Break ◽  
Crossing Over ◽  
Gene Repertoire ◽  
Evolutionary Trajectory ◽  
Dna Double Strand Break ◽  
Saccharomycodes Ludwigii ◽  
Fitness Benefits ◽  
Normal Meiosis ◽  
Break Formation

AbstractMeiotic recombination is a ubiquitous function of sexual reproduction throughout eukaryotes. Here we report that recombination is extremely suppressed during meiosis in the yeast speciesSaccharomycodes ludwigii. DNA double-strand break formation, processing and repair are required for normal meiosis but do not lead to crossing over. Although the species has retained an intact meiotic gene repertoire, genetic and population analyses suggest the exceptionally rare occurrence of meiotic crossovers. We propose thatSd. ludwigiihas followed a unique evolutionary trajectory that possibly derives fitness benefits from the combination of frequent fertilization within the meiotic tetrad with the absence of meiotic recombination.

scholarly journals ATR is a multifunctional regulator of male mouse meiosis

2017 ◽  
Author(s):  
Alexander Widger ◽  
Shantha K Mahadevaiah ◽  
Julian Lange ◽  
Elias Ellnati ◽  
Jasmin Zohren ◽  
...  
Keyword(s):  
Dna Damage ◽  
Male Mouse ◽  
Germ Line ◽  
Strand Break ◽  
Phosphatidylinositol 3 Kinase ◽  
Homologous Chromosomes ◽  
Dna Double Strand Break ◽  
Surveillance Mechanism ◽  
Chromosome Axis ◽  
Deficient Mice

Meiotic cells undergo genetic exchange between homologous chromosomes through programmed DNA double-strand break (DSB) formation, recombination and synapsis1, 2. In mice, the DNA damage-regulated phosphatidylinositol-3-kinase-like kinase (PIKK) ATM regulates all of these processes3-6. However, the meiotic functions of another major PIKK, ATR, have remained elusive, because germ line-specific depletion of this kinase is challenging. Using an efficient conditional strategy, we uncover roles for ATR in male mouse prophase I progression. Deletion of ATR causes chromosome axis fragmentation and germ cell elimination at mid pachynema. ATR is required for homologous synapsis, in a manner genetically dissociable from DSB formation. In addition, ATR regulates loading of recombinases RAD51 and DMC1 to DSBs and maintenance of recombination foci on synapsed and asynapsed chromosomes. Mid pachytene spermatocyte elimination in ATR deficient mice cannot be rescued by deletion of ATM and the third DNA damage-regulated PIKK, PRKDC, consistent with the existence of a PIKK-independent surveillance mechanism in the mammalian germ line. Our studies identify ATR as a multifunctional regulator of mouse meiosis.

scholarly journals Genome Duplication Increases Meiotic Recombination Frequency: A Saccharomyces cerevisiae Model

2020 ◽  
Author(s):  
Ou Fang ◽  
Lin Wang ◽  
Yuxin Zhang ◽  
Jixuan Yang ◽  
Qin Tao ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Meiotic Recombination ◽  
Genome Stability ◽  
Genome Duplication ◽  
Genetic Recombination ◽  
Recombination Frequency ◽  
Abiotic Factors ◽  
Strand Break ◽  
Homologous Chromosomes ◽  
Almost All

Abstract Genetic recombination characterized by reciprocal exchange of genes on paired homologous chromosomes is the most prominent event in meiosis of almost all sexually reproductive organisms. It contributes to genome stability by ensuring the balanced segregation of paired homologs in meiosis, and it is also the major driving factor in generating genetic variation for natural and artificial selection. Meiotic recombination is subjected to the control of a highly stringent and complex regulating process and meiotic recombination frequency (MRF) may be affected by biological and abiotic factors such as sex, gene density, nucleotide content, and chemical/temperature treatments, having motivated tremendous researches for artificially manipulating MRF. Whether genome polyploidization would lead to a significant change in MRF has attracted both historical and recent research interests; however, tackling this fundamental question is methodologically challenging due to the lack of appropriate methods for tetrasomic genetic analysis, thus has led to controversial conclusions in the literature. This article presents a comprehensive and rigorous survey of genome duplication-mediated change in MRF using Saccharomyces cerevisiae as a eukaryotic model. It demonstrates that genome duplication can lead to consistently significant increase in MRF and rate of crossovers across all 16 chromosomes of S. cerevisiae, including both cold and hot spots of MRF. This ploidy-driven change in MRF is associated with weakened recombination interference, enhanced double-strand break density, and loosened chromatin histone occupation. The study illuminates a significant evolutionary feature of genome duplication and opens an opportunity to accelerate response to artificial and natural selection through polyploidization.

scholarly journals Cooperative Roles of Vertebrate Fbh1 and Blm DNA Helicases in Avoidance of Crossovers during Recombination Initiated by Replication Fork Collapse

2007 ◽  
Vol 27 (8) ◽  
pp. 2812-2820 ◽  
Author(s):  
Masaoki Kohzaki ◽  
Atsushi Hatanaka ◽  
Eiichiro Sonoda ◽  
Mitsuyoshi Yamazoe ◽  
Koji Kikuchi ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Sister Chromatid ◽  
Sister Chromatid Exchange ◽  
Replication Fork ◽  
Strand Break ◽  
Dna Helicase ◽  
Dna Helicases ◽  
Homologous Chromosomes ◽  
Dna Damaging Agents ◽  
Replication Fork Arrest

ABSTRACT Fbh1 (F-box DNA helicase 1) orthologues are conserved from Schizosaccharomyces pombe to chickens and humans. Here, we report the disruption of the FBH1 gene in DT40 cells. Although the yeast fbh1 mutant shows an increase in sensitivity to DNA damaging agents, FBH1 − / − DT40 clones show no prominent sensitivity, suggesting that the loss of FBH1 might be compensated by other genes. However, FBH1 − / − cells exhibit increases in both sister chromatid exchange and the formation of radial structures between homologous chromosomes without showing a defect in homologous recombination. This phenotype is reminiscent of BLM − / − cells and suggests that Fbh1 may be involved in preventing extensive strand exchange during homologous recombination. In addition, disruption of RAD54, a major homologous recombination factor in FBH1 − / − cells, results in a marked increase in chromosome-type breaks (breaks on both sister chromatids at the same place) following replication fork arrest. Further, FBH1 BLM cells showed additive increases in both sister chromatid exchange and the formation of radial chromosomes. These data suggest that Fbh1 acts in parallel with Bloom helicase to control recombination-mediated double-strand-break repair at replication blocks and to reduce the frequency of crossover.

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