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Proceedings of the National Academy of... Dec 1983Both nonreciprocal and reciprocal mitotic recombination are enhanced by the recessive mutant spo11-1, which was previously shown to affect meiosis by decreasing... (Comparative Study)
Comparative Study
Both nonreciprocal and reciprocal mitotic recombination are enhanced by the recessive mutant spo11-1, which was previously shown to affect meiosis by decreasing recombination and increasing nondisjunction. The mitotic effects are not distributed equally in all chromosomal regions. The genotypes of mitotic recombinants in spo11-1/spo11-1 diploid cells provide further evidence that widely spaced chromosomal markers undergo coincident conversion in mitosis.
Topics: Genotype; Heterozygote; Meiosis; Mitosis; Mutation; Recombination, Genetic; Saccharomyces cerevisiae; Species Specificity
PubMed: 6369322
DOI: 10.1073/pnas.80.24.7566 -
PloS One 2013In the majority of diploid eukaryotes, each meiotic process generates four haploid gametes with each containing a single recombinant nucleus. In some species and/or some...
In the majority of diploid eukaryotes, each meiotic process generates four haploid gametes with each containing a single recombinant nucleus. In some species and/or some meiotic processes, aneuploid or diploid gametes can also be generated due to chromosomal non-disjunction and/or the co-packaging of two of the four haploid nuclei into the same gamete. Here we show that another process is involved in generating genotypes of sexual progeny from a hybrid cross between two divergent lineages of the human fungal pathogen Cryptococcus neoformans. Through micro-dissection of 1358 basidiospores from 194 basidia and genotyping using 33 co-dominant genetic markers, the genotypes of all 230 germinated basidiospores from 94 basidia were obtained. The minimum haploid genotypes required to constitute the observed genotypes from each basidium were then inferred. Our results demonstrated that more than four haploid nuclear genotypes are required to explain the observed genotypes of basidiospores in seven of the 94 basidia. Our results suggest that mitotic recombination within basidia must be involved to produce the observed genotypes in these seven basidia. The mitotic recombination likely includes both chromosomal loss and crossing over. This novel recombination process could play an important role in generating the genotypic and phenotypic diversities of this important human pathogen.
Topics: Chromosomes, Fungal; Crossing Over, Genetic; Cryptococcus neoformans; Haplotypes; Hybridization, Genetic; Mitosis; Models, Genetic; Recombination, Genetic; Spores, Fungal
PubMed: 23690954
DOI: 10.1371/journal.pone.0062790 -
G3 (Bethesda, Md.) Dec 2022Sex Ratio chromosomes in Drosophila pseudoobscura are selfish X chromosome variants associated with 3 nonoverlapping inversions. In the male germline, Sex Ratio...
Sex Ratio chromosomes in Drosophila pseudoobscura are selfish X chromosome variants associated with 3 nonoverlapping inversions. In the male germline, Sex Ratio chromosomes distort the segregation of X and Y chromosomes (99:1), thereby skewing progeny sex ratio. In the female germline, segregation of Sex Ratio chromosomes is mendelian (50:50), but nonoverlapping inversions strongly suppress recombination establishing a 26-Mb haplotype (constituting ∼20% of the haploid genome). Rare crossover events located between nonoverlapping inversions can disrupt this haplotype, and recombinants have sometimes been found in natural populations. We recently reported on the first lab-generated Sex Ratio recombinants occurring at a rate of 0.0012 crossovers per female meiosis. An improved experimental design presented here reveals that these recombination events were at least 4 times more frequent than previously estimated. Furthermore, recombination events were strongly clustered, indicating that the majority arose from mitotic exchange in female germline stem cells and not from meiotic crossing-over in primary oocytes. Finally, asymmetric recovery of complementary recombinants was consistent with unequal exchange causing the recombination-induced viability defects. Incorporating these experimental results into population models for Sex Ratio chromosome evolution provided a substantially better fit to natural population frequencies and allowed maintenance of the highly differentiated 26-Mb Sex Ratio haplotype without invoking strong epistatic selection. This study provides the first estimate of spontaneous mitotic exchange for naturally occurring chromosomes in Drosophila female germline stem cells, reveals a much higher Sex Ratio chromosome recombination rate, and develops a mathematical model that accurately predicts the rarity of recombinant Sex Ratio chromosomes in natural populations.
Topics: Animals; Drosophila; Sex Ratio; Oogonial Stem Cells; Sex Chromosomes; Meiosis; Recombination, Genetic
PubMed: 36194019
DOI: 10.1093/g3journal/jkac264 -
Genes & Development Jul 2006In budding yeast, there are two RecA homologs: Rad51 and Dmc1. While Rad51 is involved in both mitotic and meiotic recombination, Dmc1 participates specifically in...
In budding yeast, there are two RecA homologs: Rad51 and Dmc1. While Rad51 is involved in both mitotic and meiotic recombination, Dmc1 participates specifically in meiotic recombination. Here, we describe a meiosis-specific protein (Hed1) with a novel Rad51 regulatory function. Several observations indicate that Hed1 attenuates Rad51 activity when Dmc1 is absent. First, although double-strand breaks are normally poorly repaired in the dmc1 mutant, repair becomes efficient when Hed1 is absent, and this effect depends on Rad51. Second, Rad51 and Hed1 colocalize as foci on meiotic chromosomes, and chromosomal localization of Hed1 depends on Rad51. Third, production of Hed1 in vegetative cells inhibits Rad51-dependent recombination events. Fourth, the Hed1 protein shows an interaction with Rad51 in the yeast two-hybrid protein system. We propose that Hed1 provides a mechanism to ensure the coordinated action of Rad51 and Dmc1 during meiosis, by down-regulating Rad51 activity when Dmc1 is unavailable.
Topics: Chromosomes, Fungal; DNA Damage; DNA Repair; Down-Regulation; Fungal Proteins; Meiosis; Mitosis; Mutation; Rad51 Recombinase; Recombination, Genetic; Saccharomycetales
PubMed: 16818607
DOI: 10.1101/gad.1422506 -
Nucleic Acids Research Mar 2010RAD51, a key protein in the homologous recombinational DNA repair (HRR) pathway, is the major strand-transferase required for mitotic recombination. An important early... (Review)
Review
RAD51, a key protein in the homologous recombinational DNA repair (HRR) pathway, is the major strand-transferase required for mitotic recombination. An important early step in HRR is the formation of single-stranded DNA (ss-DNA) coated by RPA (a ss-DNA-binding protein). Displacement of RPA by RAD51 is highly regulated and facilitated by a number of different proteins known as the 'recombination mediators'. To assist these recombination mediators, a second group of proteins also is required and we are defining these proteins here as 'recombination co-mediators'. Defects in either recombination mediators or co-mediators, including BRCA1 and BRCA2, lead to impaired HRR that can genetically be complemented for (i.e. suppressed) by overexpression of RAD51. Defects in HRR have long been known to contribute to genomic instability leading to tumor development. Since genomic instability also slows cell growth, precancerous cells presumably require genomic re-stabilization to gain a growth advantage. RAD51 is overexpressed in many tumors, and therefore, we hypothesize that the complementing ability of elevated levels of RAD51 in tumors with initial HRR defects limits genomic instability during carcinogenic progression. Of particular interest, this model may also help explain the high frequency of TP53 mutations in human cancers, since wild-type p53 represses RAD51 expression.
Topics: Animals; DNA Repair; Genes, p53; Genomic Instability; Humans; Models, Genetic; Mutation; Neoplasms; Rad51 Recombinase; Recombination, Genetic
PubMed: 19942681
DOI: 10.1093/nar/gkp1063 -
Proceedings of the National Academy of... May 2003A transgenic mouse has been created that provides a powerful tool for revealing genetic and environmental factors that modulate mitotic homologous recombination. The...
A transgenic mouse has been created that provides a powerful tool for revealing genetic and environmental factors that modulate mitotic homologous recombination. The fluorescent yellow direct-repeat (FYDR) mice described here carry two different copies of expression cassettes for truncated coding sequences of the enhanced yellow fluorescent protein (EYFP), arranged in tandem. Homologous recombination between these repeated elements can restore full-length EYFP coding sequence to yield a fluorescent phenotype, and the resulting fluorescent recombinant cells are rapidly quantifiable by flow cytometry. Analysis of genomic DNA from recombined FYDR cells shows that this mouse model detects gene conversions, and based on the arrangement of the integrated recombination substrate, unequal sister-chromatid exchanges and repair of collapsed replication forks are also expected to reconstitute EYFP coding sequence. The rate of spontaneous recombination in primary fibroblasts derived from adult ear tissue is 1.3 +/- 0.1 per 106 cell divisions. Interestingly, the rate is approximately 10-fold greater in fibroblasts derived from embryonic tissue. We observe an approximately 15-fold increase in the frequency of recombinant cells in cultures of ear fibroblasts when exposed to mitomycin C, which is consistent with the ability of interstrand crosslinks to induce homologous recombination. In addition to studies of recombination in cultured primary cells, the frequency of recombinant cells present in skin was also measured by direct analysis of disaggregated cells. Thus, the FYDR mouse model can be used for studies of mitotic homologous recombination both in vitro and in vivo.
Topics: Animals; Bacterial Proteins; DNA Damage; DNA, Complementary; Luminescent Proteins; Mice; Mice, Transgenic; Mitosis; Recombination, Genetic; Repetitive Sequences, Nucleic Acid
PubMed: 12750464
DOI: 10.1073/pnas.1232231100 -
Environmental and Molecular Mutagenesis 1994Radiation and many chemicals have been found to induce homologous genetic recombination. Experimental systems that allow the detection and characterization of... (Review)
Review
Radiation and many chemicals have been found to induce homologous genetic recombination. Experimental systems that allow the detection and characterization of recombinagens exist in organisms as diverse as bacteria, fungi, plants, insects, and mammals. Recombination plays an important role in many biological processes, and studies of recombinagens can provide insight into underlying mechanisms. Studies of recombinagens are also of applied interest in genetic toxicology, because recombinational events in somatic cells can contribute to human disease. Clear connections have been established between mitotic recombination and the etiology of some cancers. This article briefly reviews two aspects of the induction of genetic recombination by radiation and chemicals--the health implications of recombinagenic effects and assays for detecting recombinagens.
Topics: Animals; Drosophila; Escherichia coli; Gene Deletion; Genes, Tumor Suppressor; Mammals; Mitosis; Models, Genetic; Mutagenesis, Site-Directed; Mutagenicity Tests; Mutagens; Recombination, Genetic; Saccharomyces cerevisiae; Salmonella typhimurium
PubMed: 8162910
DOI: 10.1002/em.2850230614 -
Yeast (Chichester, England) Oct 2006The study of double-strand break repair and homologous recombination in Saccharomyces cerevisiae meiosis has provided important information about the mechanisms... (Review)
Review
The study of double-strand break repair and homologous recombination in Saccharomyces cerevisiae meiosis has provided important information about the mechanisms involved. However, it has become clear that the resulting recombination models are only partially applicable to repair in mitotic cells, where crossover formation is suppressed. In recent years our understanding of double-strand break repair and homologous recombination in Schizosaccharomyces pombe has increased significantly, and the identification of novel pathways and genes with homologues in higher eukaryotes has increased its value as a model organism for double-strand break repair. In this review we will focus on the involvement of homologous recombination and repair in different aspects of genome stability in Sz. pombe meiosis, replication and telomere maintenance. We will also discuss anti-recombination pathways (that suppress crossover formation), non-homologous end-joining, single-strand annealing and factors that influence the choice and prevalence of the different repair pathways in Sz. pombe.
Topics: DNA Breaks, Double-Stranded; DNA Repair; Genome, Fungal; Mitosis; Recombination, Genetic; Schizosaccharomyces
PubMed: 17072889
DOI: 10.1002/yea.1414 -
Molecular & General Genetics : MGG May 1978The effect of inversions on mitotic recombination outside the inversion was studied in inversion-heterozygotes. Seven euchromatic inversions of the X-chromosome, with...
The effect of inversions on mitotic recombination outside the inversion was studied in inversion-heterozygotes. Seven euchromatic inversions of the X-chromosome, with breakpoints within the interval between two cell markers, were chosen. The size of the inverted region and the distance from the proximal breakpoint to the proximal cell marker varied. Mitotic recombination was X-ray induced in larvae and clones scored in the tergites of emerged adults. The frequency of recombinants between both cell markers and the frequency of recombinants proximal to the proximal cell marker was used to estimate the effect of interference in pairing caused by the inversions. Such an effect only occurs in small chromosome intervals. This indicates that homologous sequences are tightly paired in the interphase nuclei of somatic cells. This conclusion is derived from data based on X-ray induced mitotic recombination. The possibility of extending this conclusion to non-irradiated cells is discussed.
Topics: Animals; Chromosome Inversion; Chromosomes; Drosophila melanogaster; Female; Genes, Lethal; Mutation; Recombination, Genetic; Sex Chromosomes; X Chromosome; X-Rays
PubMed: 97512
DOI: 10.1007/BF00331007 -
Experimental Biology and Medicine... Oct 2010This report evaluates the potential of the antidepressant drug citalopram to induce homozygotization of genes previously present in a heterozygous condition, by...
This report evaluates the potential of the antidepressant drug citalopram to induce homozygotization of genes previously present in a heterozygous condition, by homologous recombination. In order to address this question, a heterozygous diploid strain of the filamentous fungus Aspergillus nidulans and the homozygotization assay were utilized. Non-cytotoxic concentrations of citalopram (50, 75 and 100 μmol/L) showed a strong recombinogenic effect in A. nidulans, inducing homozygosis of the diploid strain's nutritional markers. The genetic markers exhibited homozygotization index (HI) rates higher than 2.0 and significantly different from HI control ones. Since citalopram has been previously characterized as a DNA synthesis inhibitor, the recombinogenic potential of this antidepressant in A. nidulans may be associated with the recombinational repair of citalopram-induced DNA strand breaks.
Topics: Antidepressive Agents, Second-Generation; Aspergillus nidulans; Carcinogens; Citalopram; Crossing Over, Genetic; DNA Damage; DNA Repair; Depressive Disorder; Diploidy; Genes, Fungal; Genetic Markers; Heterozygote; Homozygote; Humans; Mitosis; Mutagens; Neoplasms; Recombination, Genetic
PubMed: 20851831
DOI: 10.1258/ebm.2010.010159