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At least 19 recordsLinked to original sources
PubMed1997

Interhomolog bias during meiotic recombination: meiotic functions promote a highly differentiated interhomolog-only pathway.

Meiotic recombination occurs preferentially between homologous nonsister chromatids rather than between sisters, opposite to the bias of mitotic recombinational repair. We have examined formation of joint molecule recombination intermediates (JMs) between homologs and between sisters in yeast strains lacking the meiotic chromosomal protein Red1, the meiotic recA homolog Dmc1, and/or mitotic recA homolog(s), Rad51, Rad55, and Rad57. Mutant phenotypes imply that most meiotic recombination occurs via an interhomolog-only pathway along which interhomolog bias is established early, prior to or during double strand break (DSB) formation, and then enforced, just at the time when DSBs initiate JM formation. A parallel, less differentiated pathway yields intersister and, probably, a few interhomolog events. Coordinate action of mitotic recA homologs as one functional unit, two functions of RED1, and an interhomolog interaction function of DMC1 are also revealed.

Adenosine Triphosphatases↗
PubMed2002

Targeted stimulation of meiotic recombination.

Meiotic recombination in Saccharomyces cerevisiae is initiated by programmed DNA double-strand breaks (DSBs), a process that requires the Spo11 protein. DSBs usually occur in intergenic regions that display open chromatin accessibility, but other determinants that control their frequencies and non-random chromosomal distribution remain obscure. We report that a Spo11 construct bearing the Gal4 DNA binding domain not only rescues spo11Delta spore inviability and catalyzes DSB formation at natural sites but also strongly stimulates DSB formation near Gal4 binding sites. At GAL2, a naturally DSB-cold locus, Gal4BD-Spo11 creates a recombinational hotspot that depends on all the other DSB gene functions, showing that the targeting of Spo11 to a specific site is sufficient to stimulate meiotic recombination that is under normal physiological control.

Binding Sites↗
PubMed1996

Meiotic recombination initiated by a double-strand break in rad50 delta yeast cells otherwise unable to initiate meiotic recombination.

Meiotic recombination in Saccharomyces cerevisiae is initiated by double- strand breaks (DSBs). We have developed a system to compare the properties of meiotic DSBs with those created by the site-specific HO endonuclease. HO endonuclease was expressed under the control of the meiotic-specific SPO13 promoter, creating a DSB at a single site on one of yeast's 16 chromosomes. In Rad+ strains the times of appearance of the HO-induced DSBs and of subsequent recombinants are coincident with those induced by normal meiotic DSBs. Physical monitoring of DNA showed that SPO13: : HO induced gene conversions both in Rad+ and in rad50 delta cells that cannot initiate normal meiotic DSBs. We find that the RAD50 gene is important, but not essential, for recombination even after a DSB has been created in a meiotic cell. In rad50 delta cells, some DSBs are not repaired until a broken chromosome has been packaged into a spore and is subsequently germinated. This suggests that a broken chromosome does not signal an arrest of progression through meiosis. The recombination defect in rad50 delta diploids is not, however, meiotic specific, as mitotic rad50 diploids, experiencing an HO-induced DSB, exhibit similar departures from wild-type recombination.

DNA, Fungal↗
PubMed2006

Clarifying the mechanics of DNA strand exchange in meiotic recombination.

During meiosis, accurate separation of maternal and paternal chromosomes requires that they first be connected to one another through homologous recombination. Meiotic recombination has many intriguing but poorly understood features that distinguish it from recombination in mitotically dividing cells, and several of these features depend on the meiosis-specific DNA strand exchange protein Dmc1 (disrupted meiotic cDNA1). Many questions about this protein have arisen since its discovery more than a decade ago, but recent genetic and biochemical breakthroughs promise to shed light on the unique behaviours and functions of this central player in the remarkable chromosome dynamics of meiosis.

Adenosine Triphosphatases↗
PubMed2006

Budding yeast Hed1 down-regulates the mitotic recombination machinery when meiotic recombination is impaired.

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.

Chromosomes, Fungal↗
PubMed1995

Meiotic recombination hotspots.

Meiotic recombination occurs more frequently in some regions of the eukaryotic genome than in others, with variations of several orders of magnitude observed in frequencies of meiotic exchange per unit physical distance. This article reviews what is known abut meiotic recombination hotspots loci, or regions that display a greater than average frequency of meiotic exchange. Hotspots have been most intensively studied in Saccharomyces cerevisiae, which is a major focus of this article. Also reviewed is the current state of knowledge regarding hotspots in other fungi, in maize, in nematodes, in mice, and in humans.

Animals↗
PubMed2003

Caenorhabditis elegans Ce-rdh-1/rad-51 functions after double-strand break formation of meiotic recombination.

During meiotic prophase 1, homologous recombination is accompanied by dynamic chromosomal changes. The Ce-rdh-1/rad-51 gene is the only bacterial recA-like gene in the nematode C. elegans genome. Upon depletion of Ce-rdh-1/rad-51 using the RNA interference method, abnormal 'kinked' chromosomes can be observed in mature oocytes at diakinesis, whereas synapsis between homologous chromosomes during the pachytene stage is normal. Following fertilization, Ce-rdh-1/rad-51-depleted embryos die early in embryogenesis, and their nuclei exhibit abnormal chromosome fragments and bridges. From epistasis analyses with Ce-spo-11 defective mutant and ionizing radiation, it is indicated that Ce-rdh-1/rad-51 functions after double-strand break (DSB) formation of meiotic recombination. Under the Ce-chk-2 defective condition, whose meiotic synapsis and meiotic recombination between homologous chromosomes are completely inhibited, the Ce-rdh-1/rad51 is normally expressed in the gonadal cells. Moreover, it seems that exogenous DSBs in the Ce-chk-2 defective nuclei at the pachytene stage can be repaired between sister chromatids in a Ce-rdh-1/rad-51-dependent manner. These results indicate that Ce-rdh-1/rad51 functions after both endogenous and exogenous DSB formation during meiosis, but not as 'pairing centers' for meiotic synapsis.

Animals↗
PubMed1992

Correlation between pairing initiation sites, recombination nodules and meiotic recombination in Sordaria macrospora.

The decrease of meiotic exchanges (crossing over and conversion) in two mutants of Sordaria macrospora correlated strongly with a reduction of chiasmata and of both types of "recombination nodules." Serial section reconstruction electron microscopy was used to compare the synapsis pattern of meiotic prophase I in wild type and mutants. First, synapsis occurred but the number of synaptonemal complex initiation sites was reduced in both mutants. Second, this reduction was accompanied by, or resulted in, modifications of the pattern of synapsis. Genetic and synaptonemal complex maps were compared in three regions along one chromosome arm divided into well marked intervals. Reciprocal exchange frequencies and number of recombination nodules correlated in wild type in the three analyzed intervals, but disparity was found between the location of recombination nodules and exchanges in the mutants. Despite the twofold exchange decrease, sections of the genome such as the short arm of chromosome 2 and telomere regions were sheltered from nodule decrease and from pairing modifications. This indicated a certain amount of diversity in the control of these features and suggested that exchange frequency was dependent not only on the amount of effective pairing but also on the localization of the pairing sites, as revealed by the synaptonemal complex progression in the mutants.

Ascomycota↗
PubMed2006

Association of poly-purine/poly-pyrimidine sequences with meiotic recombination hot spots.

BACKGROUND: Meiotic recombination events have been found to concentrate in 1-2.5 kilo base regions, but these recombination hot spots do not share a consensus sequence and why they occur at specific sites is not fully understood. Some previous evidence suggests that poly-purine/poly-pyrimidine (poly-pu/py) tracts (PPTs), a class of sequence with distinctive biochemical properties, could be involved in recombination, but no general association of PPTs with meiotic recombination hot spots has previously been reported. RESULTS: We used computational methods to investigate in detail the relationship between PPTs and hot spots. We show statistical associations of PPT frequency with hot spots of meiotic recombination initiating lesions, double-strand breaks, in the genome of the yeast S. cerevisiae and with experimentally well characterized human meiotic recombination hot spots. Supporting a possible role of poly-pu/py-rich sequences in hot spot recombination, we also found that all three single nucleotide polymorphisms previously shown to be associated with human hot spot activity changes occur within sequence contexts of 14 bp or longer that are 85% or more poly-pu/py and at least 70% G/C. These polymorphisms are all close to the hot spot mid points. Comparing the sequences of experimentally characterized human hot spots with the orthologous regions of the chimpanzee genome previously shown not to contain hot spots, we found that in all five cases in which comparisons for the hot spot central regions are possible with publicly available sequence data, there are differences near the human hot spot mid points within sequences 14 bp or longer consisting of more than 80% poly-pu/py and at least 50% G/C. CONCLUSION: Our results, along with previous evidence for the unique biochemical properties and recombination-stimulating potential of poly-pu/py-rich sequences, suggest that the possible functional involvement of this type of sequence in meiotic recombination hot spots deserves further experimental exploration.

Algorithms↗
PubMed2006

HUMHOT: a database of human meiotic recombination hot spots.

Meiotic recombination occurs preferentially at certain regions in the genome referred to as hot spots. The number of hot spots known in humans has increased manifold in recent years. The identification of these hot spots in humans is of great interest to population and medical geneticists since they influence the structure of Linkage Disequilibrium and Haplotype blocks in human populations, whose patterns have applications in mapping disease genes. HUMHOT is a web-based database of Human Meiotic Recombination Hot Spots. The database comprises DNA sequences corresponding to the hot spot regions from the literature that have been mapped to a high resolution (<4 kb) in humans. It also provides flanking sequence information for the hot spot region along with references describing the hot spot. The database can be queried based on hot spot identity, chromosome position or by homology to user-defined sequences. It is also updated with new hot spot sequences as they are discovered and provides hyperlinks to commonly used tools for estimating recombination rates, performing genetic analysis and new advances in our understanding of meiotic hot spots. Public access to the HUMHOT database is available at http://www.jncasr.ac.in/humhot.

Base Sequence↗
PubMed2005

[Meiotic recombination hotspots in eukaryotes].

Meiotic recombination may occur more frequently in some regions of the eukaryotic genome. These regions are referred to as meiotic recombination hotspot loci. Genetic studies in the yeast have revealed that these hotspots contain special sites for recombination initiation and result in heterogeneous distribution of recombination (along the chromosome length or across the genome). However, the data for recombination hotspot is so far limited to organisms such as fungi, maize and human. In the present paper, we listed several typical approaches to characterizing recombination hotspots in different organisms, summarizing current progress in mapping of the meiotic recombination hotspots and discussing the factors and mechanisms for activation of eukaryotic meiotic recombination. Some unresolved questions and future prospects were also discussed.

Animals↗
PubMed1998

mei-W68 in Drosophila melanogaster encodes a Spo11 homolog: evidence that the mechanism for initiating meiotic recombination is conserved.

Meiotic recombination requires the action of several gene products in both Saccharomyces cerevisiae and Drosophila melanogaster. Genetic studies in D. melanogaster have shown that the mei-W68 gene is required for all meiotic gene conversion and crossing-over. We cloned mei-W68 using a new genetic mapping method in which P elements are used to promote crossing-over at their insertion sites. This resulted in the high-resolution mapping of mei-W68 to a <18-kb region that contains a homolog of the S. cerevisiae spo11 gene. Molecular analysis of several mutants confirmed that mei-W68 encodes an spo11 homolog. Spo11 and MEI-W68 are members of a family of proteins similar to a novel type II topoisomerase. On the basis of this and other lines of evidence, Spo11 has been proposed to be the enzymatic activity that creates the double-strand breaks needed to initiate meiotic recombination. This raises the possibility that recombination in Drosophila is also initiated by double-strand breaks. Although these homologous genes are required absolutely for recombination in both species, their roles differ in other respects. In contrast to spo11, mei-W68 is not required for synaptonemal complex formation and does have a mitotic role.

Amino Acid Sequence↗
PubMed1999

A cytoplasmic dynein heavy chain is required for oscillatory nuclear movement of meiotic prophase and efficient meiotic recombination in fission yeast.

Meiotic recombination requires pairing of homologous chromosomes, the mechanisms of which remain largely unknown. When pairing occurs during meiotic prophase in fission yeast, the nucleus oscillates between the cell poles driven by astral microtubules. During these oscillations, the telomeres are clustered at the spindle pole body (SPB), located at the leading edge of the moving nucleus and the rest of each chromosome dangles behind. Here, we show that the oscillatory nuclear movement of meiotic prophase is dependent on cytoplasmic dynein. We have cloned the gene encoding a cytoplasmic dynein heavy chain of fission yeast. Most of the cells disrupted for the gene show no gross defect during mitosis and complete meiosis to form four viable spores, but they lack the nuclear movements of meiotic prophase. Thus, the dynein heavy chain is required for these oscillatory movements. Consistent with its essential role in such nuclear movement, dynein heavy chain tagged with green fluorescent protein (GFP) is localized at astral microtubules and the SPB during the movements. In dynein-disrupted cells, meiotic recombination is significantly reduced, indicating that the dynein function is also required for efficient meiotic recombination. In accordance with the reduced recombination, which leads to reduced crossing over, chromosome missegregation is increased in the mutant. Moreover, both the formation of a single cluster of centromeres and the colocalization of homologous regions on a pair of homologous chromosomes are significantly inhibited in the mutant. These results strongly suggest that the dynein-driven nuclear movements of meiotic prophase are necessary for efficient pairing of homologous chromosomes in fission yeast, which in turn promotes efficient meiotic recombination.

Amino Acid Sequence↗
PubMed1995

Imprinted chromosomal regions of the human genome display sex-specific meiotic recombination frequencies.

BACKGROUND: Meiotic recombination events do not occur randomly along a chromosome, but appear to be restricted to specific regions. In addition, some regions in the genome undergo recombination more frequently in the germ cells of one sex than the other. Genomic imprinting, the process by which the two parental alleles of a gene are differentially marked, is another genetic phenomenon associated with inheritance from only one parent or the other. The mechanisms that control meiotic recombination and genomic imprinting are unknown, but both phenomena necessarily depend on the presence of some DNA signal sequences and/or on the structure of the surrounding chromatin domain. RESULTS: In the present study, we compared the frequencies of sex-specific recombination events in three chromosomal regions of the human genome that contain clustered imprinted genes. Alignment of the genetic and physical maps of the ZNF127-SNRPN-IPW-PAR-5-PAR-1 region on chromosome 15q11-q13 (associated with Prader-Willi and Angelman syndromes) and the IGF2-H19 region on chromosome 11p15.5 (associated with Beckwith-Wiedemann syndrome) shows that both regions recombine with very high frequency during male meiosis, and with very low frequency during female meiosis. A third region around the WT-1 gene on chromosome 11p13 also recombines with higher frequency during male meiosis. CONCLUSIONS: The results show that the two best-known imprinted regions in the human genome are characterized by significant differences in recombination frequency during male and female meioses. A third, less well-characterized, imprinted region shows a similar sex-specific bias. On the basis of these observations, we propose a model suggesting that the region-specific differential accessibility of DNA that leads to differential recombination rates during male and female meioses also leads to the male- and female-specific modification of the signal sequences that control genomic imprinting.

Base Sequence↗
PubMed2006

Molecular features of meiotic recombination hot spots.

Meiotic recombination occurs preferentially at certain regions called hot spots and is important for generating genetic diversity and proper segregation of chromosomes during meiosis. Hot spots have been characterized most extensively in yeast, mice and humans. The development of methods based on sperm typing and population genetics has facilitated rapid and high-resolution mapping of hot spots in mice and humans in recent years. With increasing information becoming available on meiotic recombination in different species, it is now possible to compare several molecular features associated with hot-spot loci. Further, there have been advances in our knowledge of the factors influencing hot-spot activity and the role that they play in structuring the genome into haplotype blocks. We review the molecular features associated with hot spots in terms of their properties and mechanisms underlying their function and distribution. A large number of these features seem to be shared among hot spots from different species suggesting common mechanisms for their formation and function.

Animals↗
PubMed1996

Sensing of DNA non-homology lowers the initiation of meiotic recombination in yeast.

BACKGROUND: Meiotic recombination between homologous chromosomes in the yeast Saccharomyces cerevisiae is initiated by the formation of DNA double-strand breaks (DSBs). The mechanism of DSB formation and the factors that determine their frequency and location have yet to be elucidated. Current studies of meiotic recombination are also concerned with the question of the functional relationship between DSB formation and the other meiotic processes of homology searching, pairing and synapsis of homologues. RESULTS: To test if DNA identity is required for high levels of DSBs and recombination, we have asked whether small DNA heterologies (140-547 bp) located within the well characterized ARG4 initiator of meiotic recombination, can affect DSB formation and gene conversion events in the ARG4 locus. The present physical and genetic analyses show that some heterologies reduced recombination frequencies without altering DSB formation, whereas others reduced both DSB and gene conversion frequencies. CONCLUSIONS: These results suggest that DNA heterologies overlapping a recombination initiator impair meiotic gene conversion at two levels. First, some heterologies affect the level of DSB formation, revealing the existence of an anti-initiation process sensing the presence of sequence non-homology between the homologous chromosomes. Second, heterologies can impair the successful processing of the recombination intermediates once DSBs are made. We present a model for interhomologue cross-talks involving chromosomal and DNA/DNA interactions.

Argininosuccinate Lyase↗
PubMed1997

Recombination occurs uniformly within the bronze gene, a meiotic recombination hotspot in the maize genome.

The bronze (bz) gene is a recombinational hotspot in the maize genome: its level of meiotic recombination per unit of physical length is > 100-fold higher than the genome's average and is the highest of any plant gene analyzed to date. Here, we examine whether recombination is also unevenly distributed within the bz gene. In yeast genes, recombination (conversion) is polarized, being higher at the end of the gene where recombination is presumably initiated. We have analyzed products of meiotic recombination between heteroallelic pairs of bz mutations in both the presence and absence of heterologies and have sequenced the recombination junction in 130 such Bz intragenic recombinants. We have found that in the absence of heterologies, recombination is proportional to physical distance across the bz gene. The simplest interpretation for this lack of polarity is that recombination is initiated randomly within the gene. Insertion mutations affect the frequency and distribution of intragenic recombination events at bz, creating hotspots and coldspots. Single base pair heterologies also affect recombination, with fewer recombination events than expected by chance occurring in regions of the bz gene with a high density of heterologies. We also provide evidence that meiotic recombination in maize is conservative, that is, it does not introduce changes, and that meiotic conversion tracts are continuous and similar in size to those in yeast.

Alleles↗
PubMed1995

Allele-dependent recombination frequency: homology requirement in meiotic recombination at the hot spot in the mouse major histocompatibility complex.

Meiotic recombination break joints in the mouse major histocompatibility complex (MHC) are clustered within short segments known as hot spots. We systematically investigated the requirement for sequence homology between two chromosomes for recombination activity at the hot spot next to the Lmp2 gene. The results indicated that a high rate of recombination required a high degree of similarity of overall genome structure at the hot spot. In particular, the same copy number of repetitive sequences within the hot spot was essential for a high frequency of recombination, suggesting that recombination in mouse meiosis is more sensitive to heterozygous deletion or insertion of DNA than to mismatches of single-base substitutions.

Alleles↗