scholarly journals Mechanistic insight into crossing over during mouse meiosis

2019 ◽  
Author(s):  
Shaun E. Peterson ◽  
Scott Keeney ◽  
Maria Jasin
Keyword(s):  
Inbred Strains ◽  
Strand Break ◽  
Crossing Over ◽  
Recombination Suppression ◽  
Heteroduplex Dna ◽  
Homologous Chromosomes ◽  
Mismatch Correction ◽  
D Loop ◽  
Loop Migration ◽  
Dna Ends

SUMMARYCharacteristics of heteroduplex DNA illuminate how strands exchange during homologous recombination, but mismatch correction can obscure them. To investigate recombination mechanisms, meiotic crossover products were analyzed at two hotspots in Msh2–/– mice containing homologous chromosomes derived from inbred strains. Recombination frequencies were unchanged in the mutant, implying that MSH2-dependent recombination suppression does not occur at this level of diversity. However, a substantial fraction of crossover products retained heteroduplex DNA in the absence of MSH2, and some also had multiple switches between parental markers suggestive of MSH2-independent correction. Recombinants appeared to reflect a biased orientation of crossover resolution, possibly stemming from asymmetry at DNA ends established in earlier intermediates. Many crossover products showed no evidence of heteroduplex DNA, suggesting dismantling by D-loop migration. Unlike the complexity of crossovers in yeast, these two modifications of the original double-strand break repair model may be sufficient to explain most meiotic crossing over in mice.

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 The Conversion Gradient at HIS4 of Saccharomyces cerevisiae. II. A Role for Mismatch Repair Directed by Biased Resolution of the Recombinational Intermediate

Genetics ◽  
1999 ◽  
Vol 153 (2) ◽  
pp. 573-583 ◽  
Author(s):  
Henriette M Foss ◽  
Kenneth J Hillers ◽  
Franklin W Stahl
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dna Synthesis ◽  
Mismatch Repair ◽  
Strand Break ◽  
Double Strand Break ◽  
Double Strand Break Repair ◽  
Holliday Junction ◽  
Crossing Over ◽  
Gradient Type ◽  
Salient Features

AbstractSalient features of recombination at ARG4 of Saccharomyces provoke a variation of the double-strand-break repair (DSBR) model that has the following features: (1) Holliday junction cutting is biased in favor of strands upon which DNA synthesis occurred during formation of the joint molecule (this bias ensures that cutting both junctions of the joint-molecule intermediate arising during DSBR usually leads to crossing over); (2) cutting only one junction gives noncrossovers; and (3) repair of mismatches that are semirefractory to mismatch repair and/or far from the DSB site is directed primarily by junction resolution. The bias in junction resolution favors restoration of 4:4 segregation when such mismatches and the directing junction are on the same side of the DSB site. Studies at HIS4 confirmed the predicted influence of the bias in junction resolution on the conversion gradient, type of mismatch repair, and frequency of aberrant 5:3 segregation, as well as the predicted relationship between mismatch repair and crossing over.

Effect of the Pairing Gene Ph1 and Premeiotic Colchicine Treatment on Intra- and Interchromosome Pairing of Isochromosomes in Common Wheat

Genetics ◽  
1998 ◽  
Vol 150 (3) ◽  
pp. 1199-1208 ◽  
Author(s):  
Juan M Vega ◽  
Moshe Feldman
Keyword(s):  
Common Wheat ◽  
Homologous Chromosome ◽  
Colchicine Treatment ◽  
Crossing Over ◽  
Meiotic Pairing ◽  
Factors Affecting ◽  
Homologous Chromosomes ◽  
Polyploid Wheat ◽  
Main Gene ◽  
Ph1 Gene

Abstract The analysis of the pattern of isochromosome pairing allows one to distinguish factors affecting presynaptic alignment of homologous chromosomes from those affecting synapsis and crossing-over. Because the two homologous arms in an isochromosome are invariably associated by a common centromere, the suppression of pairing between these arms (intrachromosome pairing) would indicate that synaptic or postsynaptic events were impaired. In contrast, the suppression of pairing between an isochromosome and its homologous chromosome (interchromosome pairing), without affecting intrachromosome pairing, would suggest that homologous presynaptic alignment was impaired. We used such an isochromosome system to determine which of the processes associated with chromosome pairing was affected by the Ph1 gene of common wheat—the main gene that restricts pairing to homologues. Ph1 reduced the frequency of interchromosome pairing without affecting intrachromosome pairing. In contrast, intrachromosome pairing was strongly reduced in the absence of the synaptic gene Syn-B1. Premeiotic colchicine treatment, which drastically decreased pairing of conventional chromosomes, reduced interchromosome but not intrachromosome pairing. The results support the hypothesis that premeiotic alignment is a necessary stage for the regularity of meiotic pairing and that Ph1 relaxes this alignment. We suggest that Ph1 acts on premeiotic alignment of homologues and homeologues as a means of ensuring diploid-like meiotic behavior in polyploid wheat.

MEIOSIS IN THE GRASSHOPPER. II. THE PRELEPTOTENE SPIRAL STAGE DURING OOGENESIS AND SPERMATOGENESIS IN MELANOPLUS FEMUR-RUBRUM

1972 ◽  
Vol 14 (2) ◽  
pp. 397-401 ◽  
Author(s):  
Kathleen Church
Keyword(s):  
Dna Synthesis ◽  
Crossing Over ◽  
Chromosome Behaviour ◽  
Homologous Chromosomes ◽  
Diploid Complement

Chromosome behaviour occurring from premeiotic DNA synthesis to leptotene of meiosis is described for both males (spermatogenesis) and females (oogenesis) in the grasshopper Melanoplus femur-rubrum. These events include a period of chromosome spiralization and contraction following premeiotic DNA synthesis and prior to leptotene. The diploid complement of chromosomes becomes visible in both sexes. No pairing between homologous chromosomes or chiasmata are observed in either sex. The results suggest that synapsis and crossing over must occur following preleptotene spiralization during spermatogenesis and oogenesis in this grasshopper.

scholarly journals End-resection at DNA double-strand breaks in the three domains of life

2013 ◽  
Vol 41 (1) ◽  
pp. 314-320 ◽  
Author(s):  
John K. Blackwood ◽  
Neil J. Rzechorzek ◽  
Sian M. Bray ◽  
Joseph D. Maman ◽  
Luca Pellegrini ◽  
...  
Keyword(s):  
Dna Repair ◽  
Homologous Recombination ◽  
Strand Break ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Homologous Chromosomes ◽  
Domains Of Life ◽  
Strand Invasion ◽  
End Resection

During DNA repair by HR (homologous recombination), the ends of a DNA DSB (double-strand break) must be resected to generate single-stranded tails, which are required for strand invasion and exchange with homologous chromosomes. This 5′–3′ end-resection of the DNA duplex is an essential process, conserved across all three domains of life: the bacteria, eukaryota and archaea. In the present review, we examine the numerous and redundant helicase and nuclease systems that function as the enzymatic analogues for this crucial process in the three major phylogenetic divisions.

A Test of the Double-Strand Break Repair Model for Meiotic Recombination in Saccharomyces cerevisiae

Genetics ◽  
1996 ◽  
Vol 144 (1) ◽  
pp. 27-41 ◽  
Author(s):  
Larry A Gilbertson ◽  
Franklin W Stahl
Keyword(s):  
Meiotic Recombination ◽  
Strand Break ◽  
Double Strand Break ◽  
Double Strand Break Repair ◽  
Holliday Junction ◽  
Single Event ◽  
Heteroduplex Dna ◽  
Holliday Junction Resolvase ◽  
Break Repair ◽  
Two Sides

Abstract We tested predictions of the double-strand break repair (DSBR) model for meiotic recombination by examining the segregation patterns of small palindromic insertions, which frequently escape mismatch repair when in heteroduplex DNA. The palindromes flanked a well characterized DSB site at the ARC4 locus. The “canonical” DSBR model, in which only 5′ ends are degraded and resolution of the four-stranded intermediate is by Holliday junction resolvase, predicts that hDNA will frequently occur on both participating chromatids in a single event. Tetrads reflecting this configuration of hDNA were rare. In addition, a class of tetrads not predicted by the canonical DSBR model was identified. This class represented events that produced hDNA in a “trans” configuration, on opposite strands of the same duplex on the two sides of the DSB site. Whereas most classes of convertant tetrads had typical frequencies of associated crossovers, tetrads with trans hDNA were parental for flanking markers. Modified versions of the DSBR model, including one that uses a topoisomerase to resolve the canonical DSBR intermediate, are supported by these data.

Induction of recombination between homologous and diverged DNAs by double-strand gaps and breaks and role of mismatch repair

1994 ◽  
Vol 14 (7) ◽  
pp. 4802-4814
Author(s):  
S D Priebe ◽  
J Westmoreland ◽  
T Nilsson-Tillgren ◽  
M A Resnick
Keyword(s):  
Gene Conversion ◽  
Mismatch Repair ◽  
Sequence Divergence ◽  
Strand Break ◽  
Mismatch Repair Gene ◽  
Repair Gene ◽  
Heteroduplex Dna ◽  
Dna Mismatch ◽  
Spontaneous Recombination ◽  
The Impact

Sequence homology is expected to influence recombination. To further understand mechanisms of recombination and the impact of reduced homology, we examined recombination during transformation between plasmid-borne DNA flanking a double-strand break (DSB) or gap and its chromosomal homolog. Previous reports have concentrated on spontaneous recombination or initiation by undefined lesions. Sequence divergence of approximately 16% reduced transformation frequencies by at least 10-fold. Gene conversion patterns associated with double-strand gap repair of episomal plasmids or with plasmid integration were analyzed by restriction endonuclease mapping and DNA sequencing. For episomal plasmids carrying homeologous DNA, at least one input end was always preserved beyond 10 bp, whereas for plasmids carrying homologous DNA, both input ends were converted beyond 80 bp in 60% of the transformants. The system allowed the recovery of transformants carrying mixtures of recombinant molecules that might arise if heteroduplex DNA--a presumed recombination intermediate--escapes mismatch repair. Gene conversion involving homologous DNAs frequently involved DNA mismatch repair, directed to a broken strand. A mutation in the PMS1 mismatch repair gene significantly increased the fraction of transformants carrying a mixture of plasmids for homologous DNAs, indicating that PMS1 can participate in DSB-initiated recombination. Since nearly all transformants involving homeologous DNAs carried a single recombinant plasmid in both Pms+ and Pms- strains, stable heteroduplex DNA appears less likely than for homologous DNAs. Regardless of homology, gene conversion does not appear to occur by nucleolytic expansion of a DSB to a gap prior to recombination. The results with homeologous DNAs are consistent with a recombinational repair model that we propose does not require the formation of stable heteroduplex DNA but instead involves other homology-dependent interactions that allow recombination-dependent DNA synthesis.

Mismatch repair of heteroduplex DNA intermediates of extrachromosomal recombination in mammalian cells

1994 ◽  
Vol 14 (1) ◽  
pp. 400-406
Author(s):  
W P Deng ◽  
J A Nickoloff
Keyword(s):  
Dna Replication ◽  
Mismatch Repair ◽  
Mammalian Cells ◽  
Strand Break ◽  
Wild Type ◽  
Heteroduplex Dna ◽  
Frameshift Mutations ◽  
Single Strand Annealing ◽  
Extrachromosomal Recombination ◽  
Strand Annealing

Previous work indicated that extrachromosomal recombination in mammalian cells could be explained by the single-strand annealing (SSA) model. This model predicts that extrachromosomal recombination leads to nonconservative crossover products and that heteroduplex DNA (hDNA) is formed by annealing of complementary single strands. Mismatched bases in hDNA may subsequently be repaired to wild-type or mutant sequences, or they may remain unrepaired and segregate following DNA replication. We describe a system to examine the formation and mismatch repair of hDNA in recombination intermediates. Our results are consistent with extrachromosomal recombination occurring via SSA and producing crossover recombinant products. As predicted by the SSA model, hDNA was present in double-strand break-induced recombination intermediates. By placing either silent or frameshift mutations in the predicted hDNA region, we have shown that mismatches are efficiently repaired prior to DNA replication.

scholarly journals Regulating chromosomal movement by the cochaperone FKB-6 ensures timely pairing and synapsis

2017 ◽  
Vol 216 (2) ◽  
pp. 393-408 ◽  
Author(s):  
Benjamin Alleva ◽  
Nathan Balukoff ◽  
Amy Peiper ◽  
Sarit Smolikove
Keyword(s):  
Nuclear Envelope ◽  
Chromosome Pairing ◽  
Meiotic Prophase ◽  
Homologous Chromosome ◽  
Strand Break ◽  
Crossing Over ◽  
Chromosome Movement ◽  
Microtubule Network ◽  
Homologous Chromosome Pairing ◽  
Proper Movement

In meiotic prophase I, homologous chromosome pairing is promoted through chromosome movement mediated by nuclear envelope proteins, microtubules, and dynein. After proper homologue pairing has been established, the synaptonemal complex (SC) assembles along the paired homologues, stabilizing their interaction and allowing for crossing over to occur. Previous studies have shown that perturbing chromosome movement leads to pairing defects and SC polycomplex formation. We show that FKB-6 plays a role in SC assembly and is required for timely pairing and proper double-strand break repair kinetics. FKB-6 localizes outside the nucleus, and in its absence, the microtubule network is altered. FKB-6 is required for proper movement of dynein, increasing resting time between movements. Attenuating chromosomal movement in fkb-6 mutants partially restores the defects in synapsis, in agreement with FKB-6 acting by decreasing chromosomal movement. Therefore, we suggest that FKB-6 plays a role in regulating dynein movement by preventing excess chromosome movement, which is essential for proper SC assembly and homologous chromosome pairing.

scholarly journals The Arabidopsis HOP2 Gene Has a Role in Preventing illegitimate Exchanges between Nonhomologous Chromosomes

2021 ◽  
Author(s):  
YIsell Farahani-Tafreshi ◽  
Chun Wei ◽  
Peilu Gan ◽  
Jenya Daradur ◽  
C. Daniel Riggs ◽  
...  
Keyword(s):  
Active Role ◽  
Crossing Over ◽  
Wild Type ◽  
Positive Role ◽  
Homologous Chromosomes ◽  
Chromosome Synapsis ◽  
Radiation Induced ◽  
Nonhomologous Chromosome ◽  
Chromosome Exchanges

Meiotic homologous chromosomes pair up and undergo crossing over. In many eukaryotes both intimate pairing and crossing over require the induction of double stranded breaks (DSBs) and subsequent repair via Homologous Recombination (HR). In these organisms, two key proteins are the recombinases RAD51 and DMC1. Recombinase-modulators HOP2 and MND1 have been identified as proteins that assist RAD51 and DMC1 and are needed to promote stabilized pairing. We have probed the nature of the genetic lesions seen in hop2 mutants and looked at the role of HOP2 in the fidelity of genetic exchanges. Using γH2AX as a marker for unrepaired DSBs we found that hop2-1 and mnd1 mutants have different appearance/disappearance for DSBs than wild type, but all DSBs are repaired by mid-late pachytene. Therefore, the bridges and fragments seen from metaphase I onward are due to mis-repaired DSBs, not unrepaired ones. Studying Arabidopsis haploid meiocytes we found that wild type haploids produced the expected five univalents, but hop2-1 haploids suffered many illegitimate exchanges that were stable enough to produce bridged chromosomes during segregation. Our results suggest that HOP2 has a significant active role in preventing nonhomologous associations. We also found evidence that HOP2 plays a role in preventing illegitimate exchanges during repair of radiation-induced DSBs in rapidly dividing petal cells. Thus, HOP2 plays both a positive role in promoting homologous chromosome synapsis and a separable role in preventing nonhomologous chromosome exchanges. Possible mechanisms for this second important role are discussed.

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