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PubMed2006

Crossover frequency and synaptonemal complex length: their variability and effects on human male meiosis.

In this study, immunocytogenetics has been used in combination with the subtelomere-specific multiplex-fluorescent in-situ hybridization (stM-FISH) assay to identify 4681 autosomal synaptonemal complexes (SCs) of two fertile men. Comparisons of crossover maps for each individual SC between two men with extremely different meiotic crossover frequencies show that a low crossover frequency results in (i) a higher frequency of XY pairs and of small SCs without MLH1 foci and (ii) lower frequency of crossovers in the proximity of centromeres. In both cases, the bivalents which most frequently lacked MLH1 foci were the XY pair and the SC21. Analysis of SC length showed that SC arms can be longer or shorter than the corresponding mitotic one. Moreover, for a given SC, the variation in length found in one arm was independent of the variation observed in the other one (e.g. SC1p arms are longer than SC1q arms). The results confirmed that reduction in the crossover frequency may increase the risk of achiasmate small bivalents and that interindividual differences in crossover frequency could explain the variability in the frequencies of aneuploidy in human sperm. How MLH1 foci are positioned within the SC is discussed based on detailed MLH1 foci distributions and interfoci distances. Finally, evidence that the variation of the SC arm length may reflect the abundance of open and of compact chromatin fibers in the arm is shown.

Chromosome Mapping↗
PubMed1991

Temporal comparison of recombination and synaptonemal complex formation during meiosis in S. cerevisiae.

In synchronous cultures of S. cerevisiae undergoing meiosis, an early event in the meiotic recombination pathway, site-specific double strand breaks (DSBs), occurs early in prophase, in some instances well before tripartite synaptonemal complex (SC) begins to form. This observation, together with previous results, supports the view that events involving DSBs are required for SC formation. We discuss the possibility that the mitotic pathway for recombinational repair of DSBs served as the primordial mechanism for connecting homologous chromosomes during the evolution of meiosis. DSBs disappear during the period when tripartite SC structure is forming and elongating (zygotene); presumably, they are converted to another type of recombination intermediate. Neither DSBs nor mature recombinant molecules are present when SCs are full length (pachytene). Mature reciprocally recombinant molecules arise at the end of or just after pachytene. We suggest that the SC might coordinate recombinant maturation with other events of meiosis.

Chromatin↗
PubMed1994

Synaptonemal complex aberrations in the pseudoautosomal region of X, Y chromosomes in irradiated hamsters.

The effects of X-radiation, bleomycin and amsacrine (m-AMSA) on the meiotic chromosomes of male Armenian hamsters were determined by electron microscopic analysis of synaptonemal complex (SC) damage. Pachytene stage cells were analyzed 5 or 6 days following their treatment at putative preleptotene-leptotene stages of meiosis. Of the multiple types of SC aberrations observed to be significantly increased over control levels, lateral element breakage and synaptic anomalies were most prevalent. The focus of these studies was on the sex chromosomes which, in the Armenian hamster, reveal an unusually well-defined pseudoautosomal region. In the XY pair, radiation and chemical treatments caused certain forms of structural and synaptic anomalies which appeared to be preferentially localized to telomeric and/or crossover regions. The nature of these specific aberrations, involving breakage, bridge formation and asynapsis, is not well understood; however, their distributions are suggestive of possible relationships with sites and processes of crossing over.

Amsacrine↗
PubMed1995

Two-dimensional spreads of synaptonemal complexes from solanaceous plants. VI. High-resolution recombination nodule map for tomato (Lycopersicon esculentum).

We have produced a high-resolution physical recombination map for tomato chromosomes by determining the frequency and distribution of recombination nodules (RNs) on tomato synaptonemal complexes (SCs). We present evidence that there is a 1:1 relationship between RNs and chiasmata. Every SC has at least one RN. There are no RNs at the ends of SCs, in kinetochores, or in the heterochromatic short arm of SC 2 that carries the nucleolus organizer. RNs are more common per unit length of SC in euchromatin compared with SC in heterochromatin . The average number of RNs per SC and the average number of RNs per SC arm are directly correlated with the length of SC in euchromatin. When SCs have only one RN, that RN occurs on the long arm more frequently than predicted based on SC arm length. Patterns of multiple Rns on SCs indicate RN (crossover) interference. Rns probably can occur anywhere on SCs in euchromatin, but RNs are not distributed randomly along SCs in euchromatin or in heterochromatin. The lengths of tomato's physical recombination (RN) map, classical genetic linkage map, and molecular linkage map all differ from each other for a variety of reasons.

Chi-Square Distribution↗
PubMed1992

DMC1: a meiosis-specific yeast homolog of E. coli recA required for recombination, synaptonemal complex formation, and cell cycle progression.

DMC1 is a new meiosis-specific yeast gene. Dmc1 protein is structurally similar to bacterial RecA proteins. dmc1 mutants are defective in reciprocal recombination, accumulate double-strand break (DSB) recombination intermediates, fail to form normal synaptonemal complex (SC), and arrest late in meiotic prophase. dmc1 phenotypes are consistent with a functional relationship between Dmc1 and RecA, and thus eukaryotic and prokaryotic mechanisms for homology recognition and strand exchange may be related. dmc1 phenotypes provide further evidence that recombination and SC formation are interrelated processes and are consistent with a requirement for DNA-DNA interactions during SC formation. dmc1 mutations confer prophase arrest. Additional evidence suggests that arrest occurs at a meiosis-specific cell cycle "checkpoint" in response to a primary defect in prophase chromosome metabolism. DMC1 is homologous to yeast's RAD51 gene, supporting the view that mitotic DSB repair has been recruited for use in meiotic chromosome metabolism.

Amino Acid Sequence↗
PubMed1999

Localization of single- and low-copy sequences on tomato synaptonemal complex spreads using fluorescence in situ hybridization (FISH).

Fluorescence in situ hybridization (FISH) is a powerful means by which single- and low-copy DNA sequences can be localized on chromosomes. Compared to the mitotic metaphase chromosomes that are normally used in FISH, synaptonemal complex (SC) spreads (hypotonically spread pachytene chromosomes) have several advantages. SC spreads (1) are comparatively free of debris that can interfere with probe penetration, (2) have relatively decondensed chromatin that is highly accessible to probes, and (3) are about ten times longer than their metaphase counterparts, which permits FISH mapping at higher resolution. To investigate the use of plant SC spreads as substrates for single-copy FISH, we probed spreads of tomato SCs with two single-copy sequences and one low-copy sequence (ca. 14 kb each) that are associated with restriction fragment length polymorphism (RFLP) markers on SC 11. Individual SCs were identified on the basis of relative length, arm ratio, and differential staining patterns after combined propidium iodide (PI) and 4', 6-diamidino-2-phenylindole (DAPI) staining. In this first report of single-copy FISH to SC spreads, the probe sequences were unambiguously mapped on the long arm of tomato SC 11. Coupled with data from earlier studies, we determined the distance in micrometers, the number of base pairs, and the rates of crossing over between these three FISH markers. We also observed that the order of two of the FISH markers is reversed in relation to their order on the molecular linkage map. SC-FISH mapping permits superimposition of markers from molecular linkage maps directly on pachytene chromosomes and thereby contributes to our understanding of the relationship between chromosome structure, gene activity, and recombination.

Chromatin↗
PubMed1997

Human synaptonemal complex protein 1 (SCP1): isolation and characterization of the cDNA and chromosomal localization of the gene.

Synaptonemal complexes (SCs) are structures that are formed between homologous chromosomes (homologs) during meiotic prophase. They consist of two proteinaceous axes, one along each homolog, that are connected along their length by numerous transverse filaments (TFs). The cDNA encoding one major component of TFs of SCs of the rat, rnSCP1, has recently been isolated and characterized. In this paper we describe the isolation and characterization of the cDNA encoding the human protein homologous to rnSCP1, hsSCP1. hsSCP1 and rnSCP1 have 75% amino acid identity. The most prominent structural features and amino acid sequence motifs of rnSCP1 have been conserved in hsSCP1. Most probably, hsSCP1 is functionally homologous to rnSCP1. The hsSCP1 gene was assigned to human chromosome 1p12-p13 by fluorescence in situ hybridization.

Amino Acid Sequence↗
PubMed1977

Synaptonemal complexes in antheridia of Achlya ambisexualis E87.

This is the first report of longitudinal sections of synaptonemal complexes in oömycetous fungi. These indicators of meiosis were observed in antheridial nuclei of Achlya ambisexualis E87. They were attached to a platelike structure at the inner membrane of the nuclear envelope. The lateral elements were separated from each other by an average distance of 160nm. These results provide new ultrastructural evidence for gametangial meiosis in Oömycetes.

Fungi↗
PubMed1977

Mouse chromosome translocations: visualization and analysis by electron microscopy of the synaptonemal complex.

Pachytene chromosomes of mice heterozygous for known translocations are clearly depicted by configurations of the synaptonemal complexes in spread (whole mount) preparations. In one autosomal and two X-autosome translocations analyzed, breakpoints are identifiable; localization by measurement agrees with mitotic data and shows the translocations to be reciprocal. Synapsis with the Y is inhibited in one translocation in which the breakpoint is the pairing region of the X.

Animals↗
PubMed1987

Synaptonemal complex damage as a measure of chemical mutagen effects on mammalian germ cells.

As heritable chromosome anomalies are implicated in a variety of human disabilities, their induction in germ cells by environmental chemicals is viewed as a threat to health (National Research Council, 1982; Hook, 1983). Synaptonemal complex (SC) analysis is a novel approach for the detection of germ-line chromosomal damage. This sensitive cytological procedure reveals induced structural damage and pairing abnormalities in SCs of meiotic prophase chromosomes, together with other germ-line toxic effects, in the testes of rodents treated with mitomycin C and cyclophosphamide. Our results demonstrate the effectiveness of SC analysis as a rapid and practical in vivo germ-line mutagen assay that lacks many of the short-comings of existing tests.

Animals↗
PubMed1997

Protein-protein interactions in the synaptonemal complex.

In mammalian systems, an approximately M(r) 30,000 Cor1 protein has been identified as a major component of the meiotic prophase chromosome cores, and a M(r) 125,000 Syn1 protein is present between homologue cores where they are synapsed and form the synaptonemal complex (SC). Immunolocalization of these proteins during meiosis suggests possible homo- and heterotypic interactions between the two as well as possible interactions with yet unrecognized proteins. We used the two-hybrid system in the yeast Saccharomyces cerevisiae to detect possible protein-protein associations. Segments of hamsters Cor1 and Syn1 proteins were tested in various combinations for homo- and heterotypic interactions. In the cause of Cor1, homotypic interactions involve regions capable of coiled-coil formation, observation confirmed by in vitro affinity coprecipitation experiments. The two-hybrid assay detects no interaction of Cor1 protein with central and C-terminal fragments of Syn1 protein and no homotypic interactions involving these fragments of Syn1. Hamster Cor1 and Syn1 proteins both associate with the human ubiquitin-conjugation enzyme Hsubc9 as well as with the hamster Ubc9 homologue. The interactions between SC proteins and the Ubc9 protein may be significant for SC disassembly, which coincides with the repulsion of homologs by late prophase I, and also for the termination of sister centromere cohesiveness at anaphase II.

Animals↗
PubMed1992

[Electron microscopic analysis of synaptonemal complexes of male laboratory mice exposed during the period of embryogenesis in the vicinity of the Chernobyl Nuclear Power Station].

Four male mice were shown to have decreased fertility among 74 laboratory male mice exposed in the Chernobyl APP area during embryogenesis. Electron microscopic analysis of synaptonemal complexes (SC) of at zygotene-diplotene and light-optic analysis of chromosome aberrations at diakinesis-metaphase 1 demonstrated the presence of interchromosome translocations in autosomal chromosomes, and also intrachromosome translocations in two of four animals. The frequency of chromosome translocations in SC preparations was on the average 1.8 times higher than their frequency at the diakinesis-metaphase 1 stage. High percentage of cells in which associations of sex bivalent axes (XY) with the axes of autosomal bivalents were observed in the SC preparations and reduced fertility in the animals studied confirmed the Forejt's hypothesis that such associations caused the arrest of cells at pachytene and, as a consequence, disturbed the process of embryogenesis.

Accidents↗
PubMed1993

Synaptonemal complex analysis of a reciprocal translocation, rcp(20;24) (q17;q25), in a subfertile bull.

A reciprocal translocation was identified in a subfertile artificial insemination bull. Somatic chromosome investigation of G-banded metaphases demonstrated a 60,XY,rcp(20;24)(q17;q25) karyotype for the carrier. Synaptonemal complex analysis of the translocation by electron microscopy revealed an irregular pairing behavior of the chromosome axes involved, which resulted in a variety of configurations at pachytene. Not only was the expected quadrivalent configuration present, but also a trivalent plus univalent and two heteromorphic bivalents. Most common was an incompletely or completely paired quadrivalent configuration, which was non-homologously paired. XY association with the multivalent was seen only rarely. Histological analysis of testicular tissue showed meiotic arrest in some tubules. However, the semen picture was normal.

Animals↗
PubMed1994

[Synaptonemal complex analysis of 13/17 Robertsonian translocation in the domestic pig].

G and C-banding study of the chromosomes of several male pigs, indicate that all of these pigs carry rob(13;17). The karyotype is 2n = 37, XY, rob (13;17). In this paper, silverstained Synaptonemal Complexes (SCs) in surface-spread pachytene nuclei from these pigs are analysed by electron microscope. The result is as follows: Robertsonian translocation metacentrics rob (13;17) paired with homologous acrocentrics (13,17), forming a trivalent. All trivalents are in a cis configuration and there is delayed pairing in the trivalent. We measured every part of trivalent in the different stage of prophase (based on the morphology of XY-bivalent). It is shown that accompanying with rob(13;17) formation there has been a deletion in the proximal part of 13, 17 translocation chromosome. In the process of synapsis, the length adjustment phenomenon in the trivalent occurred: a. There is nonhomologous synapsis between the two short arms of the acrocentrics (13;17). The length of short SC varied. b. The position of the short SC, which is on the long SC(homologous synapsis of rob(13; 17) and 13, 17) moved, from one-fourth of long SC to one-tenth of it, near the end of 17 arm. These phenomenon is the result of a gradual length adjustment of lateral elements of 13,17 to the lateral element of the rob (13;17). We has discussed the mechanism of the trivalent synaptic adjustment, and it's important use to control the chiasmata and disjunction of the chromosomes.

Animals↗
PubMed2004

Inter-sex variation in synaptonemal complex lengths largely determine the different recombination rates in male and female germ cells.

Meiotic chromosomes in human oocytes are packaged differently than in spermatocytes at the pachytene stage of meiosis I, when crossing-over takes place. Thus the meiosis-specific pairing structure, the synaptonemal complex (SC), is considerably longer in oocytes in comparison to spermatocytes. The aim of the present study was to examine the influence of this length factor on meiotic recombination in male and female human germ cells. The positions of crossovers were identified by the DNA mismatch repair protein MLH1. Spermatocytes have approximately 50 crossovers per cell in comparison to more than 70 in oocytes. Analyses of inter-crossover distances (and presumptively crossover interference) along SCs suggested that while there might be inter-individual variation, there was no consistent difference between sexes. Thus the higher rate of recombination in human oocytes is not a consequence of more closely spaced crossovers along the SCs. The rate of recombination per unit length of SC is higher in spermatocytes than oocytes. However, when the so-called obligate chiasma is excluded from the analysis, then the rates of recombination per unit length of SC are essentially identical in the two sexes. Our analyses indicate that the inter-sex difference in recombination is largely a consequence of the difference in meiotic chromosome architecture in the two sexes. We propose that SC length per se, and therefore the size of the physical platform for crossing-over (and not the DNA content) is the principal factor determining the difference in rate of recombination in male and female germ cells. A preliminary investigation of SC loop size by fluorescence in situ hybridization (FISH) indicated loops may be shorter in oocytes than in spermatocytes.

Adaptor Proteins, Signal Transducing↗
PubMed2002

[Schistosoma reflexum in a female bovine fetus with synaptonemal complex abnormalities].

In this study we present mitotic- and meiotic investigations in an anatomical abnormal bovine fetus. The abnormality could be classified as "schistosoma reflexum", which was never described in fetuses in the literature. In the mitotical chromosome preparations from fibroblast cultures the examined fetus showed no chromosomal difference in comparison to the standard synaptonemal complexes (SC) which were prepared from the fetus at the age of 92 days post coitum. In the SCs from the abnormal fetus 43.75% of the investigated cells showed abnormalities such as "loop," "nonhomologue pairing" and "multivalency" in the pairing behavior of the chromosomes. In comparison, less than 5% of the cells in normal embryos showed such abnormalities.

Animals↗
PubMed1985

Synaptonemal complex analysis of a pericentric inversion in chromosome 2 of domestic fowl, Gallus domesticus.

Electron microscopy of synaptonemal complexes in three Gallus domesticus cockerels that were heterokaryotypic for a pericentric inversion in chromosome 2 revealed a low incidence of homologous pairing and a high incidence of nonhomologous pairing. The significance of these results are related to the finding that heterokaryotypic parents have fertility rates that are normal or above normal and produce only balanced gametes. One cockerel apparently had both normal cells and cells with a heteromorphic bivalent 2 in its germ line.

Animals↗