Architecture and Dynamics of Meiotic Chromosomes

2021 ◽  
Vol 55 (1) ◽  
Author(s):  
Sarah N. Ur ◽  
Kevin D. Corbett
Keyword(s):  
Meiotic Prophase ◽  
Morphological Changes ◽  
Meiotic Chromosome ◽  
Dna Recombination ◽  
Chromosome Complement ◽  
Annual Review ◽  
Publication Date ◽  
Meiotic Chromosomes ◽  
Crystal Model ◽  
Chromosome Axis

The specialized two-stage meiotic cell division program halves a cell's chromosome complement in preparation for sexual reproduction. This reduction in ploidy requires that in meiotic prophase, each pair of homologous chromosomes (homologs) identify one another and form physical links through DNA recombination. Here, we review recent advances in understanding the complex morphological changes that chromosomes undergo during meiotic prophase to promote homolog identification and crossing over. We focus on the structural maintenance of chromosomes (SMC) family cohesin complexes and the meiotic chromosome axis, which together organize chromosomes and promote recombination. We then discuss the architecture and dynamics of the conserved synaptonemal complex (SC), which assembles between homologs and mediates local and global feedback to ensure high fidelity in meiotic recombination. Finally, we discuss exciting new advances, including mechanisms for boosting recombination on particular chromosomes or chromosomal domains and the implications of a new liquid crystal model for SC assembly and structure. Expected final online publication date for the Annual Review of Genetics, Volume 55 is November 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Molecular organization of mammalian meiotic chromosome axis revealed by expansion STORM microscopy

2019 ◽  
Vol 116 (37) ◽  
pp. 18423-18428 ◽  
Author(s):  
Huizhong Xu ◽  
Zhisong Tong ◽  
Qing Ye ◽  
Tengqian Sun ◽  
Zhenmin Hong ◽  
...  
Keyword(s):  
Meiotic Chromosome ◽  
Molecular Organization ◽  
Homologous Chromosomes ◽  
Meiotic Chromosomes ◽  
C Terminus ◽  
Stochastic Optical Reconstruction Microscopy ◽  
Optical Reconstruction ◽  
20 Nm ◽  
Chromosome Axis

During prophase I of meiosis, chromosomes become organized as loop arrays around the proteinaceous chromosome axis. As homologous chromosomes physically pair and recombine, the chromosome axis is integrated into the tripartite synaptonemal complex (SC) as this structure’s lateral elements (LEs). While the components of the mammalian chromosome axis/LE—including meiosis-specific cohesin complexes, the axial element proteins SYCP3 and SYCP2, and the HORMA domain proteins HORMAD1 and HORMAD2—are known, the molecular organization of these components within the axis is poorly understood. Here, using expansion microscopy coupled with 2-color stochastic optical reconstruction microscopy (STORM) imaging (ExSTORM), we address these issues in mouse spermatocytes at a resolution of 10 to 20 nm. Our data show that SYCP3 and the SYCP2 C terminus, which are known to form filaments in vitro, form a compact core around which cohesin complexes, HORMADs, and the N terminus of SYCP2 are arrayed. Overall, our study provides a detailed structural view of the meiotic chromosome axis, a key organizational and regulatory component of meiotic chromosomes.

scholarly journals The Multiple Roles of Cohesin in Meiotic Chromosome Morphogenesis and Pairing

2009 ◽  
Vol 20 (3) ◽  
pp. 1030-1047 ◽  
Author(s):  
Gloria A. Brar ◽  
Andreas Hochwagen ◽  
Ly-sha S. Ee ◽  
Angelika Amon
Keyword(s):  
Sister Chromatid ◽  
Meiotic Prophase ◽  
Meiotic Chromosome ◽  
Sister Chromatid Cohesion ◽  
Multiple Roles ◽  
Axis Formation ◽  
Chromatid Cohesion ◽  
Cohesin Subunit ◽  
Chromosome Axis ◽  
Segregation Of Chromosomes

Sister chromatid cohesion, mediated by cohesin complexes, is laid down during DNA replication and is essential for the accurate segregation of chromosomes. Previous studies indicated that, in addition to their cohesion function, cohesins are essential for completion of recombination, pairing, meiotic chromosome axis formation, and assembly of the synaptonemal complex (SC). Using mutants in the cohesin subunit Rec8, in which phosphorylated residues were mutated to alanines, we show that cohesin phosphorylation is not only important for cohesin removal, but that cohesin's meiotic prophase functions are distinct from each other. We find pairing and SC formation to be dependent on Rec8, but independent of the presence of a sister chromatid and hence sister chromatid cohesion. We identified mutations in REC8 that differentially affect Rec8's cohesion, pairing, recombination, chromosome axis and SC assembly function. These findings define Rec8 as a key determinant of meiotic chromosome morphogenesis and a central player in multiple meiotic events.

scholarly journals Transcription dynamically patterns the meiotic chromosome-axis interface

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Xiaoji Sun ◽  
Lingzhi Huang ◽  
Tovah E Markowitz ◽  
Hannah G Blitzblau ◽  
Doris Chen ◽  
...  
Keyword(s):  
Protein Binding ◽  
Budding Yeast ◽  
Meiotic Chromosome ◽  
Cohesin Complex ◽  
Protein Enrichment ◽  
Meiotic Chromosomes ◽  
Convergent Transcription ◽  
Chromosome Axis ◽  
Ubiquitous Presence ◽  
Axial Element

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.

scholarly journals Shugoshin is essential for meiotic prophase checkpoints in C. elegans

2018 ◽  
Author(s):  
Tisha Bohr ◽  
Christian R. Nelson ◽  
Stefani Giacopazzi ◽  
Piero Lamelza ◽  
Needhi Bhalla
Keyword(s):  
Sister Chromatid ◽  
Meiotic Prophase ◽  
Meiotic Chromosome ◽  
Sister Chromatid Cohesion ◽  
Chromosomal Protein ◽  
Loss Of Function ◽  
Chromosome Architecture ◽  
C Elegans ◽  
Meiotic Chromosomes ◽  
Chromatid Cohesion

AbstractThe conserved factor Shugoshin is dispensable in C. elegans for the two-step loss of sister chromatid cohesion that directs the proper segregation of meiotic chromosomes. We show that the C. elegans ortholog of Shugoshin, SGO-1, is required for checkpoint activity in meiotic prophase. This role in checkpoint function is similar to that of the meiotic chromosomal protein, HTP-3. Null sgo-1 mutants exhibit additional phenotypes similar to that of a partial loss of function allele of HTP-3: premature synaptonemal complex disassembly, the activation of alternate DNA repair pathways and an inability to recruit a conserved effector of the DNA damage pathway, HUS-1. SGO-1 localizes to pre-meiotic nuclei, when HTP-3 is present but not yet loaded onto chromosome axes, suggesting an early role in regulating meiotic chromosome metabolism. We propose that SGO-1 acts during pre-meiotic replication to ensure fully functional meiotic chromosome architecture, rendering these chromosomes competent for checkpoint activity and normal progression of meiotic recombination. Given that most research on Shugoshin has been focused on its regulation of sister chromatid cohesion in meiosis, this novel role may be conserved but previously uncharacterized in other organisms. Further, our findings expand the repertoire of Shugoshin’s functions beyond coordinating regulatory activities at the centromere.

scholarly journals Cohesin Smc1β determines meiotic chromatin axis loop organization

2008 ◽  
Vol 180 (1) ◽  
pp. 83-90 ◽  
Author(s):  
Ivana Novak ◽  
Hong Wang ◽  
Ekaterina Revenkova ◽  
Rolf Jessberger ◽  
Harry Scherthan ◽  
...  
Keyword(s):  
Meiotic Chromosome ◽  
Model Systems ◽  
Chromatin Loop ◽  
Loop Size ◽  
Chromatin Loops ◽  
Meiotic Chromosomes ◽  
Chromatid Cohesion ◽  
Axis Extension ◽  
Chromosome Axis ◽  
Structural Maintenance Of Chromosomes

Meiotic chromosomes consist of proteinaceous axial structures from which chromatin loops emerge. Although we know that loop density along the meiotic chromosome axis is conserved in organisms with different genome sizes, the basis for the regular spacing of chromatin loops and their organization is largely unknown. We use two mouse model systems in which the postreplicative meiotic chromosome axes in the mutant oocytes are either longer or shorter than in wild-type oocytes. We observe a strict correlation between chromosome axis extension and a general and reciprocal shortening of chromatin loop size. However, in oocytes with a shorter chromosome axis, only a subset of the chromatin loops is extended. We find that the changes in chromatin loop size observed in oocytes with shorter or longer chromosome axes depend on the structural maintenance of chromosomes 1β (Smc1β), a mammalian chromosome–associated meiosis-specific cohesin. Our results suggest that in addition to its role in sister chromatid cohesion, Smc1β determines meiotic chromatin loop organization.

scholarly journals The rec8 gene of Schizosaccharomyces pombe is involved in linear element formation, chromosome pairing and sister-chromatid cohesion during meiosis.

Genetics ◽  
1995 ◽  
Vol 141 (1) ◽  
pp. 61-73
Author(s):  
M Molnar ◽  
J Bähler ◽  
M Sipiczki ◽  
J Kohli
Keyword(s):  
Schizosaccharomyces Pombe ◽  
Chromosome Pairing ◽  
Meiotic Recombination ◽  
Meiotic Prophase ◽  
Meiotic Chromosome ◽  
Linear Element ◽  
Meiotic Chromosomes ◽  
Sister Chromatids ◽  
Linear Elements ◽  
Chromosome Iii

Abstract The fission yeast Schizosaccharomyces pombe does not form tripartite synaptonemal complexes during meiotic prophase, but axial core-like structures (linear elements). To probe the relationship between meiotic recombination and the structure, pairing, and segregation of meiotic chromosomes, we genetically and cytologically characterized the rec8-110 mutant, which is partially deficient in meiotic recombination. The pattern of spore viability indicates that chromosome segregation is affected in the mutant. A detailed segregational analysis in the rec8-110 mutant revealed more spores disomic for chromosome III than in a wild-type strain. Aberrant segregations are caused by precocious segregation of sister chromatids at meiosis I, rather than by nondisjunction as a consequence of lack of crossovers. In situ hybridization further showed that the sister chromatids are separated prematurely during meiotic prophase. Moreover, the mutant forms aberrant linear elements and shows a shortened meiotic prophase. Meiotic chromosome pairing in interstitial and centromeric regions is strongly impaired in rec8-110, whereas the chromosome ends are less deficient in pairing. We propose that the rec8 gene encodes a protein required for linear element formation and that the different phenotypes of rec8-110 reflect direct and indirect consequences of the absence of regular linear elements.

scholarly journals Topoisomerases modulate the timing of meiotic DNA breakage and chromosome morphogenesis in Saccharomyces cerevisiae

2019 ◽  
Author(s):  
Jonna Heldrich ◽  
Xiaoji Sun ◽  
Luis A. Vale-Silva ◽  
Tovah E. Markowitz ◽  
Andreas Hochwagen
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Meiotic Recombination ◽  
Meiotic Prophase ◽  
Meiotic Chromosome ◽  
Strand Break ◽  
Temperature Sensitive ◽  
Chromosomal Dna ◽  
Meiotic Chromosomes ◽  
Chromosome Synapsis ◽  
Intergenic Regions

AbstractDuring meiotic prophase, concurrent transcription, recombination, and chromosome synapsis, place substantial topological strain on chromosomal DNA, but the role of topoisomerases in this context remains poorly defined. Here, we analyzed the roles topoisomerases I and II (Top1 and Top2) during meiotic prophase in Saccharomyces cerevisiae. We show that both topoisomerases accumulate primarily in promoter-containing intergenic regions of actively transcribing genes. Enrichment partially overlaps meiotic double-strand break (DSB) hotspots, but disruption of either topoisomerase has different effects during meiotic recombination. TOP1 disruption delays DSB induction and shortens the window of DSB accumulation by an unknown mechanism. By contrast, temperature-sensitive top2-1 mutants accumulate DSBs on synapsed chromosomes and exhibit a marked delay in meiotic chromosome remodeling. This defect results from a delay in recruiting the meiotic chromosome remodeler Pch2/TRIP13 but, unexpectedly, is not due to a loss of Top2 catalytic activity. Instead, mutant Top2-1 protein has reduced contact with chromatin but remains associated with meiotic chromosomes, and we provide evidence that this altered binding is responsible for the delay in chromosome remodeling. Our results imply independent roles for topoisomerases I and II in modulating meiotic recombination.

scholarly journals Structural damage to meiotic chromosomes impairs DNA recombination and checkpoint control in mammalian oocytes

2006 ◽  
Vol 173 (4) ◽  
pp. 485-495 ◽  
Author(s):  
Hong Wang ◽  
Christer Höög
Keyword(s):  
Structural Damage ◽  
Meiotic Chromosome ◽  
Dna Recombination ◽  
Control Mechanisms ◽  
Checkpoint Control ◽  
Early Postnatal Development ◽  
Meiotic Chromosomes ◽  
Complex Protein ◽  
Synaptonemal Complex Protein ◽  
Related Proteins

Meiosis in human oocytes is a highly error-prone process with profound effects on germ cell and embryo development. The synaptonemal complex protein 3 (SYCP3) transiently supports the structural organization of the meiotic chromosome axis. Offspring derived from murine Sycp3−/− females die in utero as a result of aneuploidy. We studied the nature of the proximal chromosomal defects that give rise to aneuploidy in Sycp3−/− oocytes and how these errors evade meiotic quality control mechanisms. We show that DNA double-stranded breaks are inefficiently repaired in Sycp3−/− oocytes, thereby generating a temporal spectrum of recombination errors. This is indicated by a strong residual γH2AX labeling retained at late meiotic stages in mutant oocytes and an increased persistence of recombination-related proteins associated with meiotic chromosomes. Although a majority of the mutant oocytes are rapidly eliminated at early postnatal development, a subset with a small number of unfinished crossovers evades the DNA damage checkpoint, resulting in the formation of aneuploid gametes.

scholarly journals Pds5 is required for homologue pairing and inhibits synapsis of sister chromatids during yeast meiosis

2009 ◽  
Vol 186 (5) ◽  
pp. 713-725 ◽  
Author(s):  
Hui Jin ◽  
Vincent Guacci ◽  
Hong-Guo Yu
Keyword(s):  
Sister Chromatid ◽  
Morphological Changes ◽  
Meiotic Chromosome ◽  
Sister Chromatid Cohesion ◽  
Strand Breaks ◽  
Meiotic Chromosomes ◽  
Sister Chromatids ◽  
Chromatid Cohesion ◽  
Cohesin Subunit ◽  
Yeast Meiosis

During meiosis, homologues become juxtaposed and synapsed along their entire length. Mutations in the cohesin complex disrupt not only sister chromatid cohesion but also homologue pairing and synaptonemal complex formation. In this study, we report that Pds5, a cohesin-associated protein known to regulate sister chromatid cohesion, is required for homologue pairing and synapsis in budding yeast. Pds5 colocalizes with cohesin along the length of meiotic chromosomes. In the absence of Pds5, the meiotic cohesin subunit Rec8 remains bound to chromosomes with only minor defects in sister chromatid cohesion, but sister chromatids synapse instead of homologues. Double-strand breaks (DSBs) are formed but are not repaired efficiently. In addition, meiotic chromosomes undergo hypercondensation. When the mitotic cohesin subunit Mcd1 is substituted for Rec8 in Pds5-depleted cells, chromosomes still hypercondense, but synapsis of sister chromatids is abolished. These data suggest that Pds5 modulates the Rec8 activity to facilitate chromosome morphological changes required for homologue synapsis, DSB repair, and meiotic chromosome segregation.

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

2016 ◽  
Author(s):  
Darpan Medhi ◽  
Alastair S. H. Goldman ◽  
Michael Lichten
Keyword(s):  
Meiotic Recombination ◽  
Chromosome Structure ◽  
Budding Yeast ◽  
Meiotic Chromosome ◽  
Major Determinant ◽  
The Other ◽  
Biochemical Mechanism ◽  
Meiotic Chromosomes ◽  
Yeast Meiosis ◽  
Chromosome Axis

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.

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