scholarly journals Crossover patterning through kinase-regulated condensation and coarsening of recombination nodules

2021 ◽  
Author(s):  
Liangyu Zhang ◽  
Weston Stauffer ◽  
David Zwicker ◽  
Abby F. Dernburg
Keyword(s):  
Synaptonemal Complex ◽  
Meiotic Recombination ◽  
Ring Domain ◽  
Homologous Chromosomes ◽  
Crossover Interference ◽  
C Elegans ◽  
Recombination Nodules

AbstractMeiotic recombination is highly regulated to ensure precise segregation of homologous chromosomes. Evidence from diverse organisms indicates that the synaptonemal complex (SC), which assembles between paired chromosomes, plays essential roles in crossover formation and patterning. Several additional “pro-crossover” proteins are also required for recombination intermediates to become crossovers. These typically form multiple foci or recombination nodules along SCs, and later accumulate at fewer, widely spaced sites. Here we report that in C. elegans CDK-2 is required to stabilize all crossover intermediates and stabilizes interactions among pro-crossover factors by phosphorylating MSH-5. Additionally, we show that the conserved RING domain proteins ZHP-3/4 diffuse along the SC and remain dynamic following their accumulation at recombination sites. Based on these and previous findings we propose a model in which recombination nodules arise through spatially restricted biomolecular condensation and then undergo a regulated coarsening process, resulting in crossover interference.

scholarly journals A compartmentalized, self-extinguishing signaling network mediates crossover control in meiosis

2017 ◽  
Author(s):  
Liangyu Zhang ◽  
Simone Köhler ◽  
Regina Rillo-Bohn ◽  
Abby F. Dernburg
Keyword(s):  
Chromosome Segregation ◽  
Meiotic Recombination ◽  
Molecular Basis ◽  
Chromosome Pair ◽  
Ring Finger ◽  
Cytological Analysis ◽  
Homologous Chromosomes ◽  
Crossover Interference ◽  
C Elegans ◽  
Ring Finger Proteins

AbstractMeiotic recombination between homologous chromosomes is tightly regulated to ensure proper chromosome segregation. Each chromosome pair typically undergoes at least one crossover event (crossover assurance) but these exchanges are also strictly limited in number and widely spaced along chromosomes (crossover interference). This has implied the existence of chromosome-wide signals that regulate crossovers, but their molecular basis remains mysterious. Here we characterize a family of four related RING finger proteins in C. elegans. These proteins are recruited to the synaptonemal complex between paired homologs, where they act as two heterodimeric complexes, likely as E3 ubiquitin ligases. Genetic and cytological analysis reveals that they act with additional components to create a self-extinguishing circuit that controls crossover designation and maturation. These proteins also act at the top of a hierarchical chromosome remodeling process that enables crossovers to direct stepwise segregation. Work in diverse phyla indicates that related mechanisms mediate crossover control across eukaryotes.

scholarly journals Meiotic recombination modulates the structure and dynamics of the synaptonemal complex during C. elegans meiosis

2017 ◽  
Author(s):  
Divya Pattabiraman ◽  
Baptiste Roelens ◽  
Alexander Woglar ◽  
Anne M. Villeneuve
Keyword(s):  
Synaptonemal Complex ◽  
Central Region ◽  
Meiotic Recombination ◽  
Meiotic Prophase ◽  
Dynamic Properties ◽  
Stable State ◽  
Dynamic State ◽  
Homologous Chromosomes ◽  
C Elegans ◽  
A Site

AbstractDuring meiotic prophase, a structure called the synaptonemal complex (SC) assembles at the interface between aligned pairs of homologous chromosomes, and crossover recombination events occur between their DNA molecules. Here we investigate the inter-relationships between these two hallmark features of the meiotic program in the nematode C. elegans, revealing dynamic properties of the SC that are modulated by recombination. We demonstrate that the SC incorporates new subunits and switches from a more highly dynamic/labile state to a more stable state as germ cells progress through the pachytene stage of meiotic prophase. We further show that the more dynamic state of the SC is prolonged in mutants where meiotic recombination is impaired. Moreover, in meiotic mutants where recombination intermediates are present in limiting numbers, SC central region subunits become preferentially stabilized on the subset of chromosome pairs that harbor a site where pro-crossover factors COSA-1 and MutSγ are concentrated. Polo-like kinase PLK-2 becomes preferentially localized to the SCs of chromosome pairs harboring recombination sites prior to the enrichment of SC central region proteins on such chromosomes, and PLK-2 is required for this enrichment to occur. Further, late pachytene nuclei in a plk-2 mutant exhibit the more highly dynamic SC state. Together our data demonstrate that crossover recombination events elicit chromosome-autonomous stabilizing effects on the SC and implicate PLK-2 in this process. We discuss how this recombination-triggered modulation of SC state might contribute to regulatory mechanisms that operate during meiosis to ensure the formation of crossovers while at the same time limiting their numbers.

scholarly journals Synaptonemal Complex dimerization regulates chromosome alignment and crossover patterning in meiosis

2020 ◽  
Author(s):  
Spencer G. Gordon ◽  
Lisa E. Kursel ◽  
Kewei Xu ◽  
Ofer Rog
Keyword(s):  
Synaptonemal Complex ◽  
Sequence Homology ◽  
Genetic Information ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Homologous Chromosomes ◽  
C Elegans ◽  
Local Sequence ◽  
Chromosome Alignment ◽  
Dimerization Interface

AbstractDuring sexual reproduction the parental homologous chromosomes find each other (pair) and align along their lengths by integrating local sequence homology with large-scale contiguity, thereby allowing for precise exchange of genetic information. The Synaptonemal Complex (SC) is a conserved zipper-like structure that assembles between the homologous chromosomes. This phase-separated interface brings chromosomes together and regulates exchanges between them. However, the molecular mechanisms by which the SC carries out these functions remain poorly understood. Here we isolated and characterized two mutations in the dimerization interface in the middle of the SC zipper in C. elegans. The mutations perturb both chromosome alignment and the regulation of genetic exchanges. Underlying the chromosome-scale phenotypes are distinct alterations to the way SC subunits interact with one another. We propose that the SC brings homologous chromosomes together through two biophysical activities: obligate dimerization that prevents assembly on unpaired chromosomes; and a tendency to phase-separate that extends pairing interactions along the entire length of the chromosomes.

scholarly journals A compartmentalized signaling network mediates crossover control in meiosis

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Liangyu Zhang ◽  
Simone Köhler ◽  
Regina Rillo-Bohn ◽  
Abby F Dernburg
Keyword(s):  
Caenorhabditis Elegans ◽  
Symmetry Breaking ◽  
Synaptonemal Complex ◽  
Chromosome Segregation ◽  
Molecular Basis ◽  
Liquid Crystalline ◽  
Ring Finger ◽  
Homologous Chromosomes ◽  
Crossover Interference ◽  
Ring Finger Proteins

During meiosis, each pair of homologous chromosomes typically undergoes at least one crossover (crossover assurance), but these exchanges are strictly limited in number and widely spaced along chromosomes (crossover interference). The molecular basis for this chromosome-wide regulation remains mysterious. A family of meiotic RING finger proteins has been implicated in crossover regulation across eukaryotes. Caenorhabditis elegans expresses four such proteins, of which one (ZHP-3) is known to be required for crossovers. Here we investigate the functions of ZHP-1, ZHP-2, and ZHP-4. We find that all four ZHP proteins, like their homologs in other species, localize to the synaptonemal complex, an unusual, liquid crystalline compartment that assembles between paired homologs. Together they promote accumulation of pro-crossover factors, including ZHP-3 and ZHP-4, at a single recombination intermediate, thereby patterning exchanges along paired chromosomes. These proteins also act at the top of a hierarchical, symmetry-breaking process that enables crossovers to direct accurate chromosome segregation.

scholarly journals SYNAPTONEMAL COMPLEX AND RECOMBINATION NODULES IN WILD-TYPE DROSOPHILA MELANOGASTER FEMALES

Genetics ◽  
1979 ◽  
Vol 92 (2) ◽  
pp. 511-541
Author(s):  
Adelaide T C Carpenter
Keyword(s):  
Drosophila Melanogaster ◽  
Synaptonemal Complex ◽  
Meiotic Recombination ◽  
Morphological Type ◽  
Wild Type ◽  
Recombination Nodule ◽  
Recombination Nodules ◽  
Recombination Processes ◽  
A Subunit ◽  
Serial Section Reconstruction

ABSTRACT Electron microscope serial section reconstruction analysis of all zygotene-pachytene nuclei of meiotic cells from three wild-type germaria (a subunit of the ovary containing the early meiotic stages arrayed in temporal developmental sequence) of Drosophila melanogaster females corroborates and extends earlier observations (CARPENTER 1975a) on the nature and sequence of ultrastructural events occurring during the time of meiotic recombination. Emphasis has been placed on (1) the time of appearance and disappearance of the synaptonemal complex (SC) and the changes in its dimensions that accompany a cell's progression through pachytene, and (2) the appearance, disappearance, number and chromosomal locations of recombination nodules (CARPENTER 1975b). For both the SC and the recombination nodule the availability of several developmental series has provided an estimate of the biological variability in the properties of these recombination-associated structures. The much more extensive data presented here substantiate the earlier hypothesis that recombination nodules occur at sites where reciprocal meiotic recombination will occur, has occurred, or is occurring. A second morphological type of recombination nodule is reported; it is suggested that the presence of the latter type of nodule may correlate with sites of gene conversion. The hypothesis that there may be two types of meiotic recombination processes is discussed.

scholarly journals The Yeast Motor Protein, Kar3p, Is Essential for Meiosis I

1997 ◽  
Vol 139 (2) ◽  
pp. 459-467 ◽  
Author(s):  
Carol A. Bascom-Slack ◽  
Dean S. Dawson
Keyword(s):  
Synaptonemal Complex ◽  
Meiotic Recombination ◽  
Molecular Motor ◽  
Motor Protein ◽  
Double Strand Breaks ◽  
Wild Type ◽  
Strand Breaks ◽  
Homologous Chromosomes ◽  
Low Levels ◽  
Meiosis I

The recognition and alignment of homologous chromosomes early in meiosis is essential for their subsequent segregation at anaphase I; however, the mechanism by which this occurs is unknown. We demonstrate here that, in the absence of the molecular motor, Kar3p, meiotic cells are blocked with prophase monopolar microtubule arrays and incomplete synaptonemal complex (SC) formation. kar3 mutants exhibit very low levels of heteroallelic recombination. kar3 mutants do produce double-strand breaks that act as initiation sites for meiotic recombination in yeast, but at levels severalfold reduced from wild-type. These data are consistent with a meiotic role for Kar3p in the events that culminate in synapsis of homologues.

scholarly journals ZHP-3 Acts at Crossovers to Couple Meiotic Recombination with Synaptonemal Complex Disassembly and Bivalent Formation in C. elegans

PLoS Genetics ◽  
2008 ◽  
Vol 4 (10) ◽  
pp. e1000235 ◽  
Author(s):  
Needhi Bhalla ◽  
David J. Wynne ◽  
Verena Jantsch ◽  
Abby F. Dernburg
Keyword(s):  
Synaptonemal Complex ◽  
Meiotic Recombination ◽  
C Elegans ◽  
Bivalent Formation

scholarly journals The synaptonemal complex has liquid crystalline properties and spatially regulates meiotic recombination factors

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Ofer Rog ◽  
Simone Köhler ◽  
Abby F Dernburg
Keyword(s):  
Signal Transduction ◽  
Synaptonemal Complex ◽  
Meiotic Recombination ◽  
Liquid Crystalline ◽  
Hydrophobic Interactions ◽  
Rapid Evolution ◽  
Three Dimensional ◽  
Homologous Chromosomes ◽  
Meiotic Progression ◽  
Meiotic Chromosomes

The synaptonemal complex (SC) is a polymer that spans ~100 nm between paired homologous chromosomes during meiosis. Its striated, periodic appearance in electron micrographs led to the idea that transverse filaments within this structure ‘crosslink’ the axes of homologous chromosomes, stabilizing their pairing. SC proteins can also form polycomplexes, three-dimensional lattices that recapitulate the periodic structure of SCs but do not associate with chromosomes. Here we provide evidence that SCs and polycomplexes contain mobile subunits and that their assembly is promoted by weak hydrophobic interactions, indicative of a liquid crystalline phase. We further show that in the absence of recombination intermediates, polycomplexes recapitulate the dynamic localization of pro-crossover factors during meiotic progression, revealing how the SC might act as a conduit to regulate chromosome-wide crossover distribution. Properties unique to liquid crystals likely enable long-range signal transduction along meiotic chromosomes and underlie the rapid evolution of SC proteins.

scholarly journals Identification of novel synaptonemal complex components in C. elegans

2020 ◽  
Vol 219 (5) ◽  
Author(s):  
Matthew E. Hurlock ◽  
Ivana Čavka ◽  
Lisa E. Kursel ◽  
Jocelyn Haversat ◽  
Matthew Wooten ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Structure Function ◽  
Synaptonemal Complex ◽  
Genetic Screens ◽  
Genetic Redundancy ◽  
Homologous Chromosomes ◽  
Superresolution Microscopy ◽  
C Elegans ◽  
Biochemical Identification

The synaptonemal complex (SC) is a tripartite protein scaffold that forms between homologous chromosomes during meiosis. Although the SC is essential for stable homologue pairing and crossover recombination in diverse eukaryotes, it is unknown how individual components assemble into the highly conserved SC structure. Here we report the biochemical identification of two new SC components, SYP-5 and SYP-6, in Caenorhabditis elegans. SYP-5 and SYP-6 are paralogous to each other and play redundant roles in synapsis, providing an explanation for why these genes have evaded previous genetic screens. Superresolution microscopy reveals that they localize between the chromosome axes and span the width of the SC in a head-to-head manner, similar to the orientation of other known transverse filament proteins. Using genetic redundancy and structure–function analyses to truncate C-terminal tails of SYP-5/6, we provide evidence supporting the role of SC in both limiting and promoting crossover formation.

scholarly journals Synaptonemal complex components are required for meiotic checkpoint function in C. elegans

2016 ◽  
Author(s):  
Tisha Bohr ◽  
Guinevere Ashley ◽  
Evan Eggleston ◽  
Kyra Firestone ◽  
Needhi Bhalla
Keyword(s):  
Synaptonemal Complex ◽  
Chromosome Segregation ◽  
Meiotic Chromosome ◽  
Checkpoint Response ◽  
Homologous Chromosomes ◽  
C Elegans ◽  
Homolog Pairing ◽  
The Stability ◽  
Complex Components

AbstractSynapsis involves the assembly of a proteinaceous structure, the synaptonemal complex (SC), between paired homologous chromosomes and is essential for proper meiotic chromosome segregation. In C. elegans, the synapsis checkpoint selectively removes nuclei with unsynapsed chromosomes by inducing apoptosis. This checkpoint depends on Pairing Centers (PCs), cis-acting sites that promote pairing and synapsis. We have hypothesized that the stability of homolog pairing at PCs is monitored by this checkpoint. Here, we report that SC components SYP-3, HTP-3, HIM-3 and HTP-1 are required for a functional synapsis checkpoint. Mutation of these components does not abolish PC function, demonstrating they are bonafide checkpoint components. Further, we identify mutant backgrounds in which the instability of homolog pairing at PCs does not correlate with the synapsis checkpoint response. Altogether, these data suggest that, in addition to homolog pairing, SC assembly may be monitored by the synapsis checkpoint.

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