scholarly journals Local chromosome context is a major determinant of crossover pathway biochemistry during budding yeast meiosis

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Darpan Medhi ◽  
Alastair SH Goldman ◽  
Michael Lichten

The budding yeast genome contains regions where meiotic recombination initiates more frequently than in others. This pattern parallels enrichment for the meiotic chromosome axis proteins Hop1 and Red1. These proteins are important for Spo11-catalyzed double strand break formation; their contribution to crossover recombination remains undefined. Using the sequence-specific VMA1-derived endonuclease (VDE) to initiate recombination in meiosis, we show that chromosome structure influences the choice of proteins that resolve recombination intermediates to form crossovers. At a Hop1-enriched locus, most VDE-initiated crossovers, like most Spo11-initiated crossovers, required the meiosis-specific MutLγ resolvase. In contrast, at a locus with lower Hop1 occupancy, most VDE-initiated crossovers were MutLγ-independent. In pch2 mutants, the two loci displayed similar Hop1 occupancy levels, and VDE-induced crossovers were similarly MutLγ-dependent. We suggest that meiotic and mitotic recombination pathways coexist within meiotic cells, and that features of meiotic chromosome structure determine whether one or the other predominates in different regions.

2016 ◽  
Author(s):  
Darpan Medhi ◽  
Alastair S. H. Goldman ◽  
Michael Lichten

AbstractMeiotic chromosomes are divided into regions of enrichment and depletion for meiotic chromosome axis proteins, in budding yeast Hop1 and Red1. These proteins are important for formation of Spo11-catalyzed DSB, but their contribution to crossover recombination is undefined. By studying meiotic recombination initiated by the sequence-specificVMA1-derived endonuclease (VDE), we show that meiotic chromosome structure helps to determine the biochemical mechanism by which recombination intermediates are resolved to form crossovers. At a Hop1-enriched locus, most VDE-initiated crossovers required the MutLγ resolvase, which forms most Spo11-initiated crossovers. In contrast, at a locus with lower Hop1 occupancy, most VDE-initiated crossovers were MutLγ-independent. Inpch2mutants, the two loci displayed similar Hop1 occupancy levels, and also displayed similar MutLγ-dependence of VDE-induced crossovers. We suggest that meiotic and mitotic recombination pathways coexist within meiotic cells, with features of meiotic chromosome structure partitioning the genome into regions where one pathway or the other predominates.


eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Alan MV West ◽  
Scott C Rosenberg ◽  
Sarah N Ur ◽  
Madison K Lehmer ◽  
Qiaozhen Ye ◽  
...  

The meiotic chromosome axis plays key roles in meiotic chromosome organization and recombination, yet the underlying protein components of this structure are highly diverged. Here, we show that ‘axis core proteins’ from budding yeast (Red1), mammals (SYCP2/SYCP3), and plants (ASY3/ASY4) are evolutionarily related and play equivalent roles in chromosome axis assembly. We first identify ‘closure motifs’ in each complex that recruit meiotic HORMADs, the master regulators of meiotic recombination. We next find that axis core proteins form homotetrameric (Red1) or heterotetrameric (SYCP2:SYCP3 and ASY3:ASY4) coiled-coil assemblies that further oligomerize into micron-length filaments. Thus, the meiotic chromosome axis core in fungi, mammals, and plants shares a common molecular architecture, and likely also plays conserved roles in meiotic chromosome axis assembly and recombination control.


2018 ◽  
Author(s):  
Hui Tian ◽  
Timothy Billings ◽  
Petko M. Petkov

AbstractIn most mammals, including mice and humans, meiotic recombination is determined by the meiosis specific histone methytransferase PRDM9, which binds to specific DNA sequences and trimethylates histone 3 at lysine-4 and lysine-36 at the adjacent nucleosomes. These actions ensure successful DNA double strand break initiation and repair that occur on the proteinaceous structure forming the chromosome axis. The process of hotspot association with the axis after their activation by PRDM9 is poorly understood. Previously, we and others have identified CXXC1, an ortholog of S. cerevisiae Spp1 in mammals, as a PRDM9 interactor. In yeast, Spp1 is a histone methyl reader that links H3K4me3 sites with the recombination machinery, promoting DSB formation. Here we investigated whether CXXC1 has a similar function in mouse meiosis. We found that CXXC1 is co-expressed and interacts with PRDM9 in mouse spermatocytes. To investigate the meiotic function of CXXC1, we created a Cxxc1 conditional knockout mouse to deplete CXXC1 before the onset of meiosis. Surprisingly, knockout mice were fertile, and the loss of CXXC1 in spermatocytes had no effect on hotspot trimethylation activity, double-strand break formation or repair. Our results demonstrate that CXXC1 is not an essential link between recombination hotspot sites and DSB machinery and that the hotspot recognition pathway in mouse is independent of CXXC1.Author SummaryMeiotic recombination increases genetic diversity by ensuring novel combination of alleles passing onto the next generation correctly. In most mammals, the meiotic recombination sites are determined by histone methyltransferase PRDM9. These sites subsequently become associated with the chromosome axis with the participation of additional proteins and undergo double strand breaks, which are repaired by homologous recombination. In Saccharomyces cerevisiae, Spp1 (ortholog of CXXC1) binds to methylated H3K4 and connects these sites with chromosome axis promoting DSB formation. However, our data suggest that even though CXXC1 interacts with PRDM9 in male germ cells, it does not play a crucial role in mouse meiotic recombination. These results indicate that, unlike in S. cerevisiae, a recombination initiation pathway that includes CXXC1 could only serve as a non-essential pathway in mouse meiotic recombination.


Chromosoma ◽  
2021 ◽  
Author(s):  
Da-Qiao Ding ◽  
Atsushi Matsuda ◽  
Kasumi Okamasa ◽  
Yasushi Hiraoka

AbstractThe structure of chromosomes dramatically changes upon entering meiosis to ensure the successful progression of meiosis-specific events. During this process, a multilayer proteinaceous structure called a synaptonemal complex (SC) is formed in many eukaryotes. However, in the fission yeast Schizosaccharomyces pombe, linear elements (LinEs), which are structures related to axial elements of the SC, form on the meiotic cohesin-based chromosome axis. The structure of LinEs has been observed using silver-stained electron micrographs or in immunofluorescence-stained spread nuclei. However, the fine structure of LinEs and their dynamics in intact living cells remain to be elucidated. In this study, we performed live cell imaging with wide-field fluorescence microscopy as well as 3D structured illumination microscopy (3D-SIM) of the core components of LinEs (Rec10, Rec25, Rec27, Mug20) and a linE-binding protein Hop1. We found that LinEs form along the chromosome axis and elongate during meiotic prophase. 3D-SIM microscopy revealed that Rec10 localized to meiotic chromosomes in the absence of other LinE proteins, but shaped into LinEs only in the presence of all three other components, the Rec25, Rec27, and Mug20. Elongation of LinEs was impaired in double-strand break-defective rec12− cells. The structure of LinEs persisted after treatment with 1,6-hexanediol and showed slow fluorescence recovery from photobleaching. These results indicate that LinEs are stable structures resembling axial elements of the SC.


2021 ◽  
Author(s):  
Ioannis A. Papaioannou ◽  
Fabien Dutreux ◽  
France A. Peltier ◽  
Hiromi Maekawa ◽  
Nicolas Delhomme ◽  
...  

AbstractMeiotic recombination is a ubiquitous function of sexual reproduction throughout eukaryotes. Here we report that recombination is extremely suppressed during meiosis in the yeast speciesSaccharomycodes ludwigii. DNA double-strand break formation, processing and repair are required for normal meiosis but do not lead to crossing over. Although the species has retained an intact meiotic gene repertoire, genetic and population analyses suggest the exceptionally rare occurrence of meiotic crossovers. We propose thatSd. ludwigiihas followed a unique evolutionary trajectory that possibly derives fitness benefits from the combination of frequent fertilization within the meiotic tetrad with the absence of meiotic recombination.


eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Xiaoji Sun ◽  
Lingzhi Huang ◽  
Tovah E Markowitz ◽  
Hannah G Blitzblau ◽  
Doris Chen ◽  
...  

Meiotic chromosomes are highly compacted yet remain transcriptionally active. To understand how chromosome folding accommodates transcription, we investigated the assembly of the axial element, the proteinaceous structure that compacts meiotic chromosomes and promotes recombination and fertility. We found that the axial element proteins of budding yeast are flexibly anchored to chromatin by the ring-like cohesin complex. The ubiquitous presence of cohesin at sites of convergent transcription provides well-dispersed points for axis attachment and thus chromosome compaction. Axis protein enrichment at these sites directly correlates with the propensity for recombination initiation nearby. A separate modulating mechanism that requires the conserved axial-element component Hop1 biases axis protein binding towards small chromosomes. Importantly, axis anchoring by cohesin is adjustable and readily displaced in the direction of transcription by the transcriptional machinery. We propose that such robust but flexible tethering allows the axial element to promote recombination while easily adapting to changes in chromosome activity.


eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Cathleen M Lake ◽  
Rachel J Nielsen ◽  
Fengli Guo ◽  
Jay R Unruh ◽  
Brian D Slaughter ◽  
...  

Meiotic recombination begins with the induction of programmed double-strand breaks (DSBs). In most organisms only a fraction of DSBs become crossovers. Here we report a novel meiotic gene, vilya, which encodes a protein with homology to Zip3-like proteins shown to determine DSB fate in other organisms. Vilya is required for meiotic DSB formation, perhaps as a consequence of its interaction with the DSB accessory protein Mei-P22, and localizes to those DSB sites that will mature into crossovers. In early pachytene Vilya localizes along the central region of the synaptonemal complex and to discrete foci. The accumulation of Vilya at foci is dependent on DSB formation. Immuno-electron microscopy demonstrates that Vilya is a component of recombination nodules, which mark the sites of crossover formation. Thus Vilya links the mechanism of DSB formation to either the selection of those DSBs that will become crossovers or to the actual process of crossing over.


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