what is synapsis in meiosis

doi: 10.1073/pnas.1117937108, Zickler, D., and Kleckner, N. (1999). 26, 51575162. Cell 154, 814826. Mol. What is the fundamental difference between mitosis and meiosis? Elife 6:e21455. Complementary mechanisms overlap to achieve controlled DSB formation: (i) Activation of DSB formation is controlled temporally by protein expression and by coordination with the cell cycle and DNA replication through the reliance on post-translational modifications; (ii) Positive and negative feedback loops provide homeostatic control of DSB levels; (iii) Locally, DSBs distribution is controlled by a pro-active mechanism of hotspot competition and a reactive mechanism of DSB interference; (iv) Finally, the window of opportunity of DSB formation is controlled at the chromosomal scale through a recombination-dependent feedback mechanism, and globally through pachytene exit. In mice, reduced SPO11 dosage leads to synaptic defects, and unsynapsed regions display elevated DSB markers (Kauppi et al., 2013). Indeed, the base of the cleaved loop would remain associated with the condensate after cleavage, and one or both ends of the DSB, capped by Spo11-oligonucleotide complexes (above), could also remain embedded within the condensate (Claeys Bouuaert et al., 2021; Figure 8B). Cell Res. Natl. Chem. We are not permitting internet traffic to Byjus website from countries within European Union at this time. doi: 10.1371/journal.pbio.0050324, Buhler, C., Gadelle, D., Forterre, P., Wang, J. C., and Bergerat, A. Genetics 146, 12651274. -, Alabdullah A.-K., Moore G., Martn A. C. (2021). The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fendo.2021.761249/full#supplementary-material, 1. Indeed, chromosome size impacts DSB formation, with smaller chromosomes experiencing higher DSB densities (Pan et al., 2011; Murakami et al., 2020). Exp. Biochem. (6) Hotspot competition (Tel1-independent) and DSB interference (Tel1-dependent) impact spatial distribution of DSB formation, which limits the coincident formation of two DSBs in cis within a 100-kb range or in trans between allelic regions of sister chromatids or homologs. 12, 12481256. Topo VIA is composed of a 5Y-CAP domain (related to the DNA-binding domain of the catabolite activator protein) and a Toprim domain (also found in type IIA topoisomerases and in primase) (Bergerat et al., 1997; Nichols et al., 1999; Corbett et al., 2007; Graille et al., 2008; Figure 3C). This indicates that homolog engagement feedback control operates at the level of SC assembly rather than recombination. When a sperm and an egg join in fertilization, the two haploid sets of chromosomes form a complete diploid set: a new genome. Genet. Mol. In addition to Spo11 and Rec102/Rec104 that jointly form the A and B subunits derived from Topo VI, the S. cerevisiae core complex has an additional subunit, Ski8, with as yet unknown functions (Figure 4B). Hotspot competition is genetically separable from DSB interference, the phenomenon whereby the formation of a DSB at one locus reduces the chances of another break in its vicinity. Tetraploid (AABB) and hexaploid (AABBDD) wheat have multiple sets of similar chromosomes, with successful meiosis and preservation of fertility relying on synapsis and crossover (CO) formation only taking place between homologous chromosomes. Elife 8:e40372. Reproduction (2017) 154(3):18195. doi: 10.1242/jcs.00048 Mre11 dimers coordinate DNA end bridging and nuclease processing in double-strand-break repair. Genet. Meiosis in Plants: sexual reproduction, genetic variation and crop improvement. Budding yeast ATM/ATR control meiotic double-strand break (DSB) levels by down-regulating Rec114, an essential component of the DSB-machinery. Cell. The location and structure of double-strand DNA breaks induced during yeast meiosis: evidence for a covalently linked DNA-protein intermediate. Plant Sci. Meiotic segregation, synapsis, and recombination checkpoint functions require physical interaction between the chromosomal proteins Red1p and Hop1p. Cell 69, 439456. Prophase I Early in prophase I, the chromosomes can be seen clearly microscopically. Interference is observed at the level of individual chromatids and depends on the DNA-damage response kinase Tel1, but hotspot competition does not (Mohibullah and Keeney, 2017). **p < 0.01 (Students t-test). Hum Reprod (1999) 14(5):126673. See this image and copyright information in PMC, Alabdullah A.-K., Borrill P., Martn A. C., Ramrez-Gonzlez R. H., Hassani-Pak K., Uauy C., et al. 19, 22452257. Axis proteins are therefore important for DSB formation, but their relationships with DSB proteins remain poorly understood at the molecular level. One level of activation is implemented by meiosis-specific transcription of genes encoding DSB proteins (SPO11, REC102, REC104, REC114, and MEI4) and meiosis-specific splicing of MER2 (Keeney, 2001, 2008). (2009). 7:e1002305. As a feeder cell to support in vitro meiosis of mouse mGSCs, we used an available immortalized Sertoli cell lines SK49 (30). doi: 10.1016/j.cub.2007.10.066, Blitzblau, H. G., and Hochwagen, A. However, whether the core complex is only recruited to the surface, or only active at the surface, remains unknown. However, it also raises new questions regarding the biophysical properties of the condensates, their assembly and disassembly mechanisms, and how these might be controlled, perhaps through post-translational modifications. Following DNA synthesis using the homolog as a repair template, the recombination structures experience one of two main outcomes (Allers and Lichten, 2001; Hunter and Kleckner, 2001; Bishop and Zickler, 2004; De Muyt et al., 2012; Pyatnitskaya et al., 2019; Figure 1B). 11 Articles, This article is part of the Research Topic, https://doi.org/10.3389/fendo.2021.761249, https://www.frontiersin.org/articles/10.3389/fendo.2021.761249/full#supplementary-material, Creative Commons Attribution License (CC BY), Center for Reproductive Medicine, Reproductive Biology Laboratory, Amsterdam Reproduction and Development Research Institute, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands. However, the in vitro-generated pachytene spermatocytes displayed incomplete synapsis of the homologous chromosomes, did not form an XY body and did not form meiotic crossovers. Elife 2:e00844. Evidence for a direct link between foci assembly in vivo and DNA-driven condensation in vitro came from mutagenesis approaches. 26, 5264. doi: 10.1007/s00294-010-0296-0, Subramanian, V. V., Zhu, X., Markowitz, T. E., Vale-Silva, L. A., San-Segundo, P. A., Hollingsworth, N. M., et al. A haploid S. cerevisiae genome contains approximately 700 loops, averaging about 15 kb each, with AT-rich sites that physically anchor a proteinaceous axis (Blat et al., 2002; Kleckner, 2006; Ito et al., 2014; Muller et al., 2018; Schalbetter et al., 2019). ATP-dependent dimerization of the GHKL domain upon sequential or simultaneous binding to gate (G) and transfer (T) DNA duplexes is communicated to the A subunit to activate DSB formation. Science 351, 943949. Nature (in press). doi: 10.26508/lsa.201800259, Lam, I., and Keeney, S. (2015). Topo VI can undergo multiple catalytic cycles without dissociation from the G-segment. Since DSB formation requires two Spo11 subunits and Topo VI has an A2B2 stoichiometry, the core complex was anticipated to form a dimer of tetramers. Alternatively, recombination structures are stabilized by the ZMM family of proteins and channeled through a pathway that produces mostly crossovers (Brner et al., 2004; Lynn et al., 2007; Pyatnitskaya et al., 2019). Processing of DNA double-strand breaks by the MRX complex in a chromatin context. In the current culture system, 1-2 M-phase cells per microscope slides were observed between day 8 to day 14 after meiotic induction (Supplementary Figure S2A). Synapsis is an event that occurs during meiosis in which homologous chromosomes pair with their counterparts and remain bound due to the exchange of genetic information. Res. Cell 16, 597608. Genes Dev. Images were analyzed using Leica Application Suite X and Image J version Java 1.8.0_77. doi: 10.1093/emboj/17.21.6412, Galbraith, A. M., and Malone, R. E. (1992). Zhou Q, Wang M, Yuan Y, Wang X, Fu R, Wan H, et al. Binding of a cell-type-specific RNA splicing factor to its target regulatory sequence. Wojtasz L, Daniel K, Roig I, Bolcun-Filas E, Xu H, Boonsanay V, et al. Nolte J, Michelmann HW, Wolf M, Wulf G, Nayernia K, Meinhardt A, et al. Roeder, G. S., Rockmill, B. M., Engebrecht, J., Thompson, E. A., and Menees, T. M. (1989). The synapsis is the pairing of a chromosome (two homologous chromosomes) during meiosis. Genes Dev. Biophys. doi: 10.1073/pnas.0711864105, Brner, G. V., Kleckner, N., and Hunter, N. (2004). Asy2/Mer2: an evolutionarily conserved mediator of meiotic recombination, pairing, and global chromosome compaction. (1982). Spo11 and the formation of DNA double-strand breaks in meiosis. The presence of a strong hotspot suppresses the DSB activity of an adjacent hotspot (Wu and Lichten, 1994; Xu et al., 1995; Keeney et al., 2014). Engagement of the second duplex activates ATP-dependent dimerization of the GHKL domain, thereby trapping the T-segment (transfer) (Corbett et al., 2007). doi: 10.1073/pnas.1406846111 The COMPASS subunit Spp1 links histone methylation to initiation of meiotic recombination. The invading strand can be ejected from the donor by action of helicases, which provides an opportunity for the DNA ends to re-anneal. Moreover, when all three copies are disrupted in Ttzip4-A1B1B2 triple mutants, COs are reduced by over 95%, suggesting that the TtZIP4-B2 copy may also affect class II COs. (A). Please enable it to take advantage of the complete set of features! Proc. Biol. The synapsed pair of homologous chromosomes are known as bivalent. Pch2 is a hexameric ring ATPase that remodels the chromosome axis protein Hop1. Hotspot competition can therefore be implemented prior to DSB formation, and RMM proteins have been suggested to constitute this limiting factor based on the fact that they are bound to the chromosome axis, which would constrain their diffusion (Panizza et al., 2011). Natl. doi: 10.4103/aja.aja_86_20, 46. Genet. Given the DNA-dependent condensation property of the RMM proteins, axis-embedded RMM condensates are a good candidate to provide this surface (Claeys Bouuaert et al., 2021). J Cell Sci (2002) 115(8):161122. Would you like email updates of new search results? Second, to provide physical connections between homologous chromosomes that allow their alignment along the meiotic spindle and their accurate segregation, thereby producing chromosomally balanced haploid gametes and maintain stable genomic contents between generations (Page and Hawley, 2003; Petronczki et al., 2003; Wilkins and Holliday, 2009; Hunter, 2015; Figure 1A). Since DSB formation is potentially dangerous, the activity of Spo11 is controlled to ensure appropriate timing, number, and distribution of breaks (Figure 9A). Early decision: meiotic crossover interference prior to stable strand exchange and synapsis. doi: 10.1016/j.cell.2010.11.015, Kim, S., Peterson, S. E., Jasin, M., and Keeney, S. (2016). 35, 759772. Finally, in the G 2 phase, the cell undergoes the final preparations for meiosis. Protein Sci. Tel1 and Mec1 mediate DSB interference in cis between different regions of the same molecule within about 100-kb range, and in trans, at allelic loci between sister chromatids (Zhang et al., 2011; Garcia et al., 2015; Fowler et al., 2018). doi: 10.1016/S0092-8674(01)00416-0, Alonso-Sarduy, L., Roduit, C., Dietler, G., and Kasas, S. (2011). Biomolecular condensates: organizers of cellular biochemistry. doi: 10.1128/mcb.12.3.1248, Corbett, K. D., Benedetti, P., and Berger, J. M. (2007). What is the relationship between DSB proteins and axis proteins? doi: 10.1110/ps.04704704, Maleki, S., Neale, M. J., Arora, C., Henderson, K. A., and Keeney, S. (2007). In vegetative cells, Ski8 localizes to the cytoplasm, but in meiotic cells it localizes to the nucleus where it interacts with Spo11 and mediates its chromosomal localization (Arora et al., 2004; Claeys Bouuaert et al., 2021). Natl. An atypical topoisomerase II from archaea with implications for meiotic recombination. Although DSB formation happens primarily within chromatin loops, most of the DSB proteins are enriched along the chromosome axis (Kugou et al., 2009; Pan et al., 2011; Panizza et al., 2011). Chiasma formation: chromatin/axis interplay and the role(s) of the synaptonemal complex. The C-terminal DNA-binding domain is dispensable for mitotic DNA repair but important for meiotic DSB formation (Furuse et al., 1998; Usui et al., 1998). Therefore, to circumvent the use of ESCs or neonatal gonad, we used mouse spermatogonia, maintained in culture as mouse male germline stem cells (mGSCs), which can be induced to undergo spermatogonial differentiation in vitro by using retinoic acid (RA) treatment (25). ATP -dependent DNA binding, unwinding, and resection by the Mre11/Rad50 complex. J. Biol. doi: 10.1007/BF00310890, Pratto, F., Brick, K., Cheng, G., Lam, G., Cloutier, J. M., Dahiya, D., et al. However, the stoichiometry of this intermediate was not determined and alternative interpretations remain plausible, including that monomeric core complexes have two independent duplex-binding sites. Figure3 Incomplete meiotic recombination and inefficient meiotic crossover formation in vitro. (A) DSBs-repair sites, marked with RAD51, are not completely resolved in in vitro- generated pachytene spermatocytes stained for SYCP3 (red), RAD51 (green) and MDC1 (white). Here, we describe our current view of the mechanism of meiotic DSB formation based on recent advances in the characterization of the structure and function of DSB proteins and discuss regulatory pathways in the light of recent models. EMBO J. Crossing-over only occur during meiosis between two non sister chromatids. Science 290, 806809. Cell 83, 783791, Seifert, F. U., Lammens, K., Stoehr, G., Kessler, B., and Hopfner, K. (2016). Isolation of mutants defective in early steps of meiotic recombination in the yeast Saccharomyces cerevisiae. doi: 10.1371/journal.pgen.1003545, Carlton, P. M., Farruggio, A. P., and Dernburg, A. F. (2006). The synapsis is the pairing of a chromosome (two homologous chromosomes) during meiosis. Insertion of long palindromes (>50 bp) within the S. cerevisiae genome generate meiotic DSB hotspots (Nasar et al., 2000). Mol. Sci. This repair mechanism was hijacked early during eukaryotic evolution to achieve two key goals in meiosis. However, after ATP hydrolysis by Rad50, a conformational change exposes the nuclease domain of Mre11 to DNA. doi: 10.1074/jbc.M101823200, Cannavo, E., and Cejka, P. (2014). Science 351, 939943. (A) The distribution of meiotic DSBs is influenced by a combination of factors that operates at various size scales (Pan et al., 2011). Chromosomes, or chromosomal regions, that lack a pairing partner, such as the largely heterologous X and Y chromosomes, show delayed meiotic DSB repair and are transcriptionally . 293, 1052410535. doi: 10.1016/S0092-8674(01)00335-X, Humphryes, N., and Hochwagen, A. doi: 10.1126/science.1086605, Paiano, J., Wu, W., Yamada, S., Sciascia, N., Callen, E., Paola Cotrim, A., et al. Of these studies only few characterized whether key meiotic events took place in vitro (2, 17). Uroz L, Templado C. Meiotic non-Disjunction Mechanisms in Human Fertile Males. (2016). Biol. A central coupler for recombination initiation linking chromosome architecture to s phase checkpoint. Thus, ZIP4-B2 in wheat accounts for the two major phenotypes reported for Ph1, promotion of homologous synapsis and suppression of homeologous COs. Keywords: Nature 510, 241246. For future investigations, undifferentiated spermatogonia that are incapable of differentiation, for instance c-kit knockout spermatogonia, could be used to ensure continued co-culture with mitotic germ cells. Cold Spring Harb. (2007). Cell 135, 662678. doi: 10.1016/S0092-8674(04)00297-1, Blat, Y., Protacio, R. U., Hunter, N., and Kleckner, N. (2002). Rad50 is an ATPase with Walker A and B motifs located at its N- and C-termini, respectively (Hopfner et al., 2001; Gobbini et al., 2016; Figure 5A). doi: 10.1093/nar/gkx1196, West, K. L., and Austin, C. A. doi: 10.1007/s00018-012-0941-5, 36. Numbered blocks indicate conserved sequence motifs (Kumar et al., 2010; Tess et al., 2017). doi: 10.1016/S1097-2765(00)80097-0, Petes, T. D. (2001). Nature 514, 122125. Meiocytes in early-stage flower buds exposed to heat stress (>35C) exhibit impaired homolog synapsis resulting in partial to complete omission of chiasmata formation. Meiosis II The second round of cell division is meiosis II, in which the goal is to separate sister chromatids. Struct. Therefore, mutants that decrease Spo11 activity experience an extended window of time for DSB formation, effectively obscuring their catalytic defects. doi: 10.1534/genetics.103.023762, Zakharyevich, K., Ma, Y., Tang, S., Hwang, P. Y. H., Boiteux, S., and Hunter, N. (2010). doi: 10.1093/nar/27.4.984, Wilkins, A. S., and Holliday, R. (2009). No use, distribution or reproduction is permitted which does not comply with these terms. 28, 420435. Figure1 Complete homologous chromosome synapsis during in vitro meiosis. Nat. Meiosis-specific RNA splicing in yeast. Tel1ATM-mediated interference suppresses clustered meiotic double-strand-break formation. Numerical constraints and feedback control of double-strand breaks in mouse meiosis. government site. Keywords: Cell. In addition, the unsynapsed portion of the X chromosome also accumulates DSBs in wild-type male mice. ATM controls meiotic double-strand-break formation. doi: 10.1038/nsmb928, Wojtasz, L., Daniel, K., Roig, I., Bolcun-Filas, E., Xu, H., Boonsanay, V., et al. The S phase is next, during which the DNA of the chromosomes is replicated. As a result of the EUs General Data Protection Regulation (GDPR). We therefore quantified the total numbers of these cell types, and meiotic M-phase cells to record the dynamics of spermatocyte numbers during the culture period, as presented in Supplementary Figure S2A. Genes Dev (2011) 25(9):95971. Asy1, a protein required for meiotic chromosome synapsis, localizes to axis-associated chromatin in Arabidopsis and Brassica . Commun. (2008). Overview of meiosis and meiotic recombination. Scale matters. Complex formation and functional versatility of Mre11 of budding yeast in recombination. The events that must take place between Mer2 phosphorylation and DSB formation are unclear, but in the light of the DNA-driven condensation properties of Rec114Mei4 and Mer2, this delay could be explained by the time required to assemble the condensates and recruit the core complex and MRX. This creates a SC structure with mobile constituents, which is thought to allow signal transmission at the interface between pairs of homologs and to regulate crossover distribution along chromosomes (Rog et al., 2017). Finally, we used antibodies against MLH1 to investigated whether meiotic crossovers were formed in vitro. If this does not occur properly, it affects the rest of meiosis as there is no crossing over so genetic recombination cannot occur. Trends Cell Biol. Meiotic association between Spo11 regulated by Rec102, Rec104 and Rec114. doi: 10.1093/nar/26.22.5157, Buhler, C., Lebbink, J. H. G., Bocs, C., Ladenstein, R., and Forterre, P. (2001).
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