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 Crossover Interference in Saccharomyces cerevisiae Requires a TID1/RDH54- and DMC1-Dependent Pathway

Genetics ◽  
2003 ◽  
Vol 163 (4) ◽  
pp. 1273-1286 ◽  
Author(s):  
Miki Shinohara ◽  
Kazuko Sakai ◽  
Akira Shinohara ◽  
Douglas K Bishop
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Meiotic Recombination ◽  
Strand Break ◽  
Tetrad Analysis ◽  
Yeast Saccharomyces Cerevisiae ◽  
Crossover Interference ◽  
Meiotic Progression ◽  
Invasion Stage ◽  
Strand Invasion ◽  
Dependent Pathway

Abstract Two RecA-like recombinases, Rad51 and Dmc1, function together during double-strand break (DSB)-mediated meiotic recombination to promote homologous strand invasion in the budding yeast Saccharomyces cerevisiae. Two partially redundant proteins, Rad54 and Tid1/Rdh54, act as recombinase accessory factors. Here, tetrad analysis shows that mutants lacking Tid1 form four-viable-spore tetrads with levels of interhomolog crossover (CO) and noncrossover recombination similar to, or slightly greater than, those in wild type. Importantly, tid1 mutants show a marked defect in crossover interference, a mechanism that distributes crossover events nonrandomly along chromosomes during meiosis. Previous work showed that dmc1Δ mutants are strongly defective in strand invasion and meiotic progression and that these defects can be partially suppressed by increasing the copy number of RAD54. Tetrad analysis is used to show that meiotic recombination in RAD54-suppressed dmc1Δ cells is similar to that in tid1; the frequency of COs and gene conversions is near normal, but crossover interference is defective. These results support the proposal that crossover interference acts at the strand invasion stage of recombination.

Recombination hot spot in the human beta-globin gene cluster: meiotic recombination of human DNA fragments in Saccharomyces cerevisiae

1985 ◽  
Vol 5 (8) ◽  
pp. 2029-2038
Author(s):  
D Treco ◽  
B Thomas ◽  
N Arnheim
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Meiotic Recombination ◽  
High Frequency ◽  
Genetic Recombination ◽  
Hot Spot ◽  
Globin Gene ◽  
Beta Globin ◽  
Beta Globin Gene ◽  
Human Dna ◽  
Yeast Meiosis

We describe a novel system for the analysis of sequence-specific meiotic recombination in Saccharomyces cerevisiae. A comparison of three adjacent restriction fragments from the human beta-globin locus revealed that one of them, previously hypothesized to contain a relative hot spot for genetic recombination, engages in reciprocal exchange during yeast meiosis significantly more frequently than either of the other two fragments. Removal of the longest of four potential Z-DNA-forming regions from this fragment does not affect the high frequency of genetic recombination.

scholarly journals A dCas9-Based System Identifies a Central Role for Ctf19 in Kinetochore-Derived Suppression of Meiotic Recombination

Genetics ◽  
2020 ◽  
Vol 216 (2) ◽  
pp. 395-408
Author(s):  
Lisa-Marie Kuhl ◽  
Vasso Makrantoni ◽  
Sarah Recknagel ◽  
Animish N. Vaze ◽  
Adele L. Marston ◽  
...  
Keyword(s):  
Meiotic Recombination ◽  
Genome Stability ◽  
Meiotic Chromosome ◽  
Homologous Chromosomes ◽  
Experimental Platform ◽  
Chromosome Missegregation ◽  
Link Type ◽  
Insight Into

In meiosis, crossover (CO) formation between homologous chromosomes is essential for faithful segregation. However, misplaced meiotic recombination can have catastrophic consequences on genome stability. Within pericentromeres, COs are associated with meiotic chromosome missegregation. In organisms ranging from yeast to humans, pericentromeric COs are repressed. We previously identified a role for the kinetochore-associated Ctf19 complex (Ctf19c) in pericentromeric CO suppression. Here, we develop a dCas9/CRISPR-based system that allows ectopic targeting of Ctf19c-subunits. Using this approach, we query sufficiency in meiotic CO suppression, and identify Ctf19 as a mediator of kinetochore-associated CO control. The effect of Ctf19 is encoded in its NH2-terminal tail, and depends on residues important for the recruitment of the Scc2-Scc4 cohesin regulator. This work provides insight into kinetochore-derived control of meiotic recombination. We establish an experimental platform to investigate and manipulate meiotic CO control. This platform can easily be adapted in order to investigate other aspects of chromosome biology.

scholarly journals Recombination hot spot in the human beta-globin gene cluster: meiotic recombination of human DNA fragments in Saccharomyces cerevisiae.

1985 ◽  
Vol 5 (8) ◽  
pp. 2029-2038 ◽  
Author(s):  
D Treco ◽  
B Thomas ◽  
N Arnheim
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Meiotic Recombination ◽  
High Frequency ◽  
Genetic Recombination ◽  
Hot Spot ◽  
Globin Gene ◽  
Beta Globin ◽  
Beta Globin Gene ◽  
Human Dna ◽  
Yeast Meiosis

We describe a novel system for the analysis of sequence-specific meiotic recombination in Saccharomyces cerevisiae. A comparison of three adjacent restriction fragments from the human beta-globin locus revealed that one of them, previously hypothesized to contain a relative hot spot for genetic recombination, engages in reciprocal exchange during yeast meiosis significantly more frequently than either of the other two fragments. Removal of the longest of four potential Z-DNA-forming regions from this fragment does not affect the high frequency of genetic recombination.

scholarly journals RAD10, an excision repair gene of Saccharomyces cerevisiae, is involved in the RAD1 pathway of mitotic recombination.

1990 ◽  
Vol 10 (6) ◽  
pp. 2485-2491 ◽  
Author(s):  
R H Schiestl ◽  
S Prakash
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Meiotic Recombination ◽  
Excision Repair ◽  
Mitotic Recombination ◽  
The Other ◽  
Gene Products ◽  
Repair Gene ◽  
Homologous Chromosomes ◽  
Intrachromosomal Recombination ◽  
Recombination Pathway

The RAD10 gene of Saccharomyces cerevisiae is required for the incision step of excision repair of UV-damaged DNA. We show that the RAD10 gene is also required for mitotic recombination. The rad10 delta mutation lowered the rate of intrachromosomal recombination of a his3 duplication in which one his3 allele has a deletion at the 3' end and the other his3 allele has a deletion at the 5' end (his3 delta 3' his3 delta 5'). The rate of formation of HIS3+ recombinants in the rad10 delta mutant was not affected by the rad1 delta mutation but decreased synergistically in the presence of the rad10 delta mutation in combination with the rad52 delta mutation. These observations indicate that the RAD1 and RAD10 genes function together in a mitotic recombination pathway that is distinct from the RAD52 recombination pathway. The rad10 delta mutation also lowered the efficiency of integration of linear DNA molecules and circular plasmids into homologous genomic sequences. We suggest that the RAD1 and RAD10 gene products act in recombination after the formation of the recombinogenic substrate. The rad1 delta and rad10 delta mutations did not affect meiotic intrachromosomal recombination of the his3 delta 3' his3 delta 5' duplication or mitotic and meiotic recombination of ade2 heteroalleles located on homologous chromosomes.

scholarly journals Nucleogenesis and origin of organelles

2008 ◽  
Vol 16 (3-4) ◽  
pp. 88-92
Author(s):  
Milanko Stupar
Keyword(s):  
Replication Fork ◽  
Genome Duplication ◽  
Genetic Recombination ◽  
Mitochondrial Gene ◽  
Strand Break ◽  
Monophyletic Origin ◽  
Double Stranded Dna ◽  
Rigid Cell Wall ◽  
Step Mechanism ◽  
Archaeal Ancestor

Division of the ancestral prokaryotic pragenome into two circular double-stranded DNA molecules by genetic recombination is a base for the future separate evolution of the nuclear and mitochondrial gene compartment. This suggests monophyletic origin of both mitochondrion and nucleus. Presumed organism which genome undergoes genetic recombination has to be searched among an aerobic, oxygen non-producing archaeon with no rigid cell wall, but a plasma membrane. Plastids evolve from an aerobic, oxygen producing proto-eukaryot, after mitoplastide genome duplication and subsequent functional segregation. In this proposal, origin of eukaryots occurs by a three-step mechanism. First, replication fork pauses and collapses generating a breakage in the genome of archaeal ancestor of eukaryots. Second, the double-strand break can be repaired intergenomically by complementary strands invasion. Third, this duplicated genome can be fissioned into two compartments by reciprocal genetic recombination. Scenario is accomplished by aberrant fission of the inner membrane surrounding separately those two compartments.

scholarly journals A dCas9/CRISPR-based targeting system identifies a central role for Ctf19 in kinetochore-derived suppression of meiotic recombination

2020 ◽  
Author(s):  
Lisa-Marie Kuhl ◽  
Vasso Makrantoni ◽  
Sarah Recknagel ◽  
Animish N. Vaze ◽  
Adele L. Marston ◽  
...  
Keyword(s):  
Meiotic Recombination ◽  
Genome Stability ◽  
Budding Yeast ◽  
Homologous Chromosomes ◽  
Experimental Platform ◽  
Chromosome Missegregation ◽  
Meiotic Crossover ◽  
Insight Into

AbstractIn meiosis, crossover formation between homologous chromosomes is essential for faithful segregation. However, improperly controlled or placed meiotic recombination can have catastrophic consequences on genome stability. Specifically, within centromeres and surrounding regions (i.e. pericentromeres), crossovers are associated with chromosome missegregation and developmental aneuploidy. In organisms ranging from yeast to humans, crossovers are repressed within (peri)centromeric regions. We previously identified a key role for the multi-subunit, kinetochore-associated Ctf19 complex (Ctf19c; the budding yeast equivalent of the human CCAN) in regulating pericentromeric crossover formation. Here, we develop a dCas9/CRISPR-based system that allows ectopic targeting of Ctf19c-subunits to a non-centromeric locus during meiosis. Using this approach, we query sufficiency in meiotic crossover suppression, and identify Ctf19 (the budding yeast homologue of vertebrate CENP-P) as a central mediator of kinetochore-associated crossover control. We show that the effect of Ctf19 is encoded in its NH2-terminal tail, and depends on residues known to be important for the recruitment of the Scc2-Scc4 cohesin regulator to kinetochores. We thus reveal a crucial determinant that links kinetochores to meiotic recombinational control. This work provides insight into localized control of meiotic recombination. Furthermore, our approach establishes a dCas9/CRISPR-based experimental platform that can be utilized to investigate and locally manipulate meiotic crossover control. This platform can easily be adapted in order to investigate other aspects of localized chromosome biology.

scholarly journals Properties of Natural Double-Strand-Break Sites at a Recombination Hotspot in Saccharomyces cerevisiae

Genetics ◽  
2003 ◽  
Vol 165 (1) ◽  
pp. 101-114 ◽  
Author(s):  
Stuart J Haring ◽  
George R Halley ◽  
Alex J Jones ◽  
Robert E Malone
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Gene Conversion ◽  
Meiotic Recombination ◽  
Strand Break ◽  
Double Strand Break ◽  
Recombination Hotspot ◽  
Recombination Hotspots ◽  
Naturally Occurring ◽  
High Level ◽  
Site Recognition

Abstract This study addresses three questions about the properties of recombination hotspots in Saccharomyces cerevisiae: How much DNA is required for double-strand-break (DSB) site recognition? Do naturally occurring DSB sites compete with each other in meiotic recombination? What role does the sequence located at the sites of DSBs play? In S. cerevisiae, the HIS2 meiotic recombination hotspot displays a high level of gene conversion, a 3′-to-5′ conversion gradient, and two DSB sites located ∼550 bp apart. Previous studies of hotspots, including HIS2, suggest that global chromosome structure plays a significant role in recombination activity, raising the question of how much DNA is sufficient for hotspot activity. We find that 11.5 kbp of the HIS2 region is sufficient to partially restore gene conversion and both DSBs when moved to another yeast chromosome. Using a variety of different constructs, studies of hotspots have indicated that DSB sites compete with one another for DSB formation. The two naturally occurring DSBs at HIS2 afforded us the opportunity to examine whether or not competition occurs between these native DSB sites. Small deletions of DNA at each DSB site affect only that site; analyses of these deletions show no competition occurring in cis or in trans, indicating that DSB formation at each site at HIS2 is independent. These small deletions significantly affect the frequency of DSB formation at the sites, indicating that the DNA sequence located at a DSB site can play an important role in recombination initiation.

Analysis of a gene conversion gradient at the HIS4 locus in Saccharomyces cerevisiae.

Genetics ◽  
1992 ◽  
Vol 132 (1) ◽  
pp. 113-123 ◽  
Author(s):  
P Detloff ◽  
M A White ◽  
T D Petes
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Gene Conversion ◽  
Mismatch Repair ◽  
Meiotic Recombination ◽  
Present Evidence ◽  
Homologous Chromosomes ◽  
A Site ◽  
His4 Gene ◽  
Heteroduplex Formation ◽  
Recombination Gene

Abstract Heteroduplexes formed between genes on homologous chromosomes are intermediates in meiotic recombination. In the HIS4 gene of Saccharomyces cerevisiae, most mutant alleles at the 5' end of the gene have a higher rate of meiotic recombination (gene conversion) than mutant alleles at the 3' end of the gene. Such gradients are usually interpreted as indicating a higher frequency of heteroduplex formation at the high conversion end of the gene. We present evidence indicating that the gradient of conversion at HIS4 primarily reflects the direction of mismatch repair rather than the frequency of heteroduplex formation. We also identify a site located between the 5' end of HIS4 and the 3' end of BIK1 that stimulates heteroduplex formation at HIS4 and BIK1.

scholarly journals Transcription of a Donor Enhances Its Use during Double-Strand Break-Induced Gene Conversion in Human Cells

2006 ◽  
Vol 26 (8) ◽  
pp. 3098-3105 ◽  
Author(s):  
Ezra Schildkraut ◽  
Cheryl A. Miller ◽  
Jac A. Nickoloff
Keyword(s):  
Gene Conversion ◽  
Genome Stability ◽  
Large Scale ◽  
Repetitive Sequences ◽  
Indirect Evidence ◽  
Strand Break ◽  
Strand Breaks ◽  
Homologous Chromosomes ◽  
Donor Choice ◽  
Donor Preference

ABSTRACT Homologous recombination (HR) mediates accurate repair of double-strand breaks (DSBs) but carries the risk of large-scale genetic change, including loss of heterozygosity, deletions, inversions, and translocations. Nearly one-third of the human genome consists of repetitive sequences, and DSB repair by HR often requires choices among several homologous repair templates, including homologous chromosomes, sister chromatids, and linked or unlinked repeats. Donor preference during DSB-induced gene conversion was analyzed by using several HR substrates with three copies of neo targeted to a human chromosome. Repair of I-SceI nuclease-induced DSBs in one neo (the recipient) required a choice between two donor neo genes. When both donors were downstream, there was no significant bias for proximal or distal donors. When donors flanked the recipient, we observed a marked (85%) preference for the downstream donor. Reversing the HR substrate in the chromosome eliminated this preference, indicating that donor choice is influenced by factors extrinsic to the HR substrate. Prior indirect evidence suggested that transcription might increase donor use. We tested this question directly and found that increased transcription of a donor enhances its use during gene conversion. A preference for transcribed donors would minimize the use of nontranscribed (i.e., pseudogene) templates during repair and thus help maintain genome stability.

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