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1.
Nature ; 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39358508

RESUMEN

A central feature of meiosis is the pairing of homologous maternal and paternal chromosomes ('homologues') along their lengths1-3. Recognition between homologues and their juxtaposition in space is mediated by axis-associated recombination complexes. Also, pairing must occur without entanglements among unrelated chromosomes. Here we examine homologue juxtaposition in real time by four-dimensional fluorescence imaging of tagged chromosomal loci at high spatio-temporal resolution in budding yeast. We discover that corresponding loci come together from a substantial distance (1.8 µm) and complete pairing in a very short time, about 6 min (thus, rapid homologue juxtaposition or RHJ). Homologue loci first move rapidly together (in 30 s, at speeds of roughly 60 nm s-1) into an intermediate stage corresponding to canonical 400 nm axis coalignment. After a short pause, crossover/non-crossover differentiation (crossover interference) mediates a second short, rapid transition that ultimately gives close pairing of axes at 100 nm by means of synaptonemal complex formation. Furthermore, RHJ (1) occurs after chromosomes acquire prophase chromosome organization, (2) is nearly synchronous over thirds of chromosome lengths, but (3) is asynchronous throughout the genome. Finally, cytoskeleton-mediated movement is important for the timing and distance of RHJ onset and for ensuring its normal progression. General implications for local and global aspects of pairing are discussed.

2.
PLoS Biol ; 22(7): e3002705, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38950075

RESUMEN

We show here that in the fungus Sordaria macrospora, the meiosis-specific HORMA-domain protein Hop1 is not essential for the basic early events of chromosome axis development, recombination initiation, or recombination-mediated homolog coalignment/pairing. In striking contrast, Hop1 plays a critical role at the leptotene/zygotene transition which is defined by transition from pairing to synaptonemal complex (SC) formation. During this transition, Hop1 is required for maintenance of normal axis structure, formation of SC from telomere to telomere, and development of recombination foci. These hop1Δ mutant defects are DSB dependent and require Sme4/Zip1-mediated progression of the interhomolog interaction program, potentially via a pre-SC role. The same phenotype occurs not only in hop1Δ but also in absence of the cohesin Rec8 and in spo76-1, a non-null mutant of cohesin-associated Spo76/Pds5. Thus, Hop1 and cohesins collaborate at this crucial step of meiotic prophase. In addition, analysis of 4 non-null mutants that lack this transition defect reveals that Hop1 also plays important roles in modulation of axis length, homolog-axis juxtaposition, interlock resolution, and spreading of the crossover interference signal. Finally, unexpected variations in crossover density point to the existence of effects that both enhance and limit crossover formation. Links to previously described roles of the protein in other organisms are discussed.


Asunto(s)
Proteínas Fúngicas , Sordariales , Complejo Sinaptonémico , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Sordariales/genética , Sordariales/metabolismo , Complejo Sinaptonémico/metabolismo , Meiosis , Profase Meiótica I , Profase , Mutación
3.
Chromosoma ; 133(2): 93-115, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38730132

RESUMEN

Meiosis is the specialized cellular program that underlies gamete formation for sexual reproduction. It is therefore not only interesting but also a fundamentally important subject for investigation. An especially attractive feature of this program is that many of the processes of special interest involve organized chromosomes, thus providing the possibility to see chromosomes "in action". Analysis of meiosis has also proven to be useful in discovering and understanding processes that are universal to all chromosomal programs. Here we provide an overview of the different historical moments when the gap between observation and understanding of mechanisms and/or roles for the new discovered molecules was bridged. This review reflects also the synergy of thinking and discussion among our three laboratories during the past several decades.


Asunto(s)
Meiosis , Humanos , Animales , Historia del Siglo XX , Historia del Siglo XXI , Historia del Siglo XIX , Cromosomas/genética
4.
bioRxiv ; 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38586034

RESUMEN

A central basic feature of meiosis is pairing of homologous maternal and paternal chromosomes ("homologs") intimately along their lengths. Recognition between homologs and their juxtaposition in space are mediated by axis-associated DNA recombination complexes. Additional effects ensure that pairing occurs without ultimately giving entanglements among unrelated chromosomes. Here we examine the process of homolog juxtaposition in real time by 4D fluorescence imaging of tagged chromosomal loci at high spatio-temporal resolution in budding yeast. We discover that corresponding loci start coming together from a quite large distance (∼1.8 µm) and progress to completion of pairing in a very short time, usually less than six minutes (thus, "rapid homolog juxtaposition" or "RHJ"). Juxtaposition initiates by motion-mediated extension of a nascent interhomolog DNA linkage, raising the possibility of a tension-mediated trigger. In a first transition, homolog loci move rapidly together (in ∼30 sec, at speeds of up to ∼60 nm/sec) into a discrete intermediate state corresponding to canonical ∼400 nm axis distance coalignment. Then, after a short pause, crossover/noncrossover differentiation (crossover interference) mediates a second short, rapid transition that brings homologs even closer together. If synaptonemal complex (SC) component Zip1 is present, this transition concomitantly gives final close pairing by axis juxtaposition at ∼100 nm, the "SC distance". We also find that: (i) RHJ occurs after chromosomes acquire their prophase chromosome organization; (ii) is nearly synchronously over thirds (or more) of chromosome lengths; but (iii) is asynchronous throughout the genome. Furthermore, cytoskeleton-mediated movement is important for the timing and distance of RHJ onset and also for ensuring normal progression. Potential implications for local and global aspects of pairing are discussed.

5.
Nucleic Acids Res ; 52(7): 3794-3809, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38340339

RESUMEN

Meiotic recombination is initiated by programmed double-strand breaks (DSBs). Studies in Saccharomyces cerevisiae have shown that, following rapid resection to generate 3' single-stranded DNA (ssDNA) tails, one DSB end engages a homolog partner chromatid and is extended by DNA synthesis, whereas the other end remains associated with its sister. Then, after regulated differentiation into crossover- and noncrossover-fated types, the second DSB end participates in the reaction by strand annealing with the extended first end, along both pathways. This second-end capture is dependent on Rad52, presumably via its known capacity to anneal two ssDNAs. Here, using physical analysis of DNA recombination, we demonstrate that this process is dependent on direct interaction of Rad52 with the ssDNA binding protein, replication protein A (RPA). Furthermore, the absence of this Rad52-RPA joint activity results in a cytologically-prominent RPA spike, which emerges from the homolog axes at sites of crossovers during the pachytene stage of the meiotic prophase. Our findings suggest that this spike represents the DSB end of a broken chromatid caused by either the displaced leading DSB end or the second DSB end, which has been unable to engage with the partner homolog-associated ssDNA. These and other results imply a close correspondence between Rad52-RPA roles in meiotic recombination and mitotic DSB repair.


Asunto(s)
Intercambio Genético , Roturas del ADN de Doble Cadena , Meiosis , Proteína Recombinante y Reparadora de ADN Rad52 , Proteína de Replicación A , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Proteína Recombinante y Reparadora de ADN Rad52/metabolismo , Proteína Recombinante y Reparadora de ADN Rad52/genética , Proteína de Replicación A/metabolismo , Proteína de Replicación A/genética , Meiosis/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Recombinación Genética , ADN de Cadena Simple/metabolismo , ADN de Cadena Simple/genética , Recombinación Homóloga/genética
6.
bioRxiv ; 2024 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-38352537

RESUMEN

The classical phenomenon of crossover interference is a one-dimensional spatial patterning process that produces evenly spaced crossovers during meiosis. Quantitative analysis of diagnostic molecules along budding yeast chromosomes reveals that this process also sets up a second, interdigitated pattern of related but longer periodicity, in a "two-tiered" patterning process. The second tier corresponds to a previously mysterious minority set of crossovers. Thus, in toto, the two tiers account for all detected crossover events. Both tiers of patterning set up spatially clustered assemblies of three types of molecules ("triads") representing the three major components of meiotic chromosomes (crossover recombination complexes and chromosome axis and synaptonemal complex components), and give focal and domainal signals, respectively. Roles are suggested. All observed effects are economically and synthetically explained if crossover patterning is mediated by mechanical forces along prophase chromosomes. Intensity levels of domainal triad components are further modulated, dynamically, by the conserved protein remodeler Pch2/TRIP13.

7.
Annu Rev Genet ; 57: 1-63, 2023 11 27.
Artículo en Inglés | MEDLINE | ID: mdl-37788458

RESUMEN

The raison d'être of meiosis is shuffling of genetic information via Mendelian segregation and, within individual chromosomes, by DNA crossing-over. These outcomes are enabled by a complex cellular program in which interactions between homologous chromosomes play a central role. We first provide a background regarding the basic principles of this program. We then summarize the current understanding of the DNA events of recombination and of three processes that involve whole chromosomes: homolog pairing, crossover interference, and chiasma maturation. All of these processes are implemented by direct physical interaction of recombination complexes with underlying chromosome structures. Finally, we present convergent lines of evidence that the meiotic program may have evolved by coupling of this interaction to late-stage mitotic chromosome morphogenesis.


Asunto(s)
Emparejamiento Cromosómico , Meiosis , Emparejamiento Cromosómico/genética , Meiosis/genética , Cromosomas/genética , ADN , Segregación Cromosómica/genética , Intercambio Genético/genética
8.
PLoS One ; 18(7): e0288611, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37440583

RESUMEN

In E. coli, double strand breaks (DSBs) are resected and loaded with RecA protein. The genome is then rapidly searched for a sequence that is homologous to the DNA flanking the DSB. Mismatches in homologous partners are rare, suggesting that RecA should rapidly reject mismatched recombination products; however, this is not the case. Decades of work have shown that long lasting recombination products can include many mismatches. In this work, we show that in vitro RecA forms readily observable recombination products when 16% of the bases in the product are mismatched. We also consider various theoretical models of mismatch-tolerant homology testing. The models test homology by comparing the sequences of Ltest bases in two single-stranded DNAs (ssDNA) from the same genome. If the two sequences pass the homology test, the pairing between the two ssDNA becomes permanent. Stringency is the fraction of permanent pairings that join ssDNA from the same positions in the genome. We applied the models to both randomly generated genomes and bacterial genomes. For both randomly generated genomes and bacterial genomes, the models show that if no mismatches are accepted stringency is ∼ 99% when Ltest = 14 bp. For randomly generated genomes, stringency decreases with increasing mismatch tolerance, and stringency improves with increasing Ltest. In contrast, in bacterial genomes when Ltest ∼ 75 bp, stringency is ∼ 99% for both mismatch-intolerant and mismatch-tolerant homology testing. Furthermore, increasing Ltest does not improve stringency because most incorrect pairings join different copies of repeats. In sum, for bacterial genomes highly mismatch tolerant homology testing of 75 bp provides the same stringency as homology testing that rejects all mismatches and testing more than ∼75 base pairs is not useful. Interestingly, in vivo commitment to recombination typically requires homology testing of ∼ 75 bp, consistent with highly mismatch intolerant testing.


Asunto(s)
ADN , Escherichia coli , Escherichia coli/genética , Escherichia coli/metabolismo , Rec A Recombinasas/genética , Rec A Recombinasas/metabolismo , Emparejamiento Base , ADN de Cadena Simple/genética , Recombinación Genética
9.
Nat Cell Biol ; 25(8): 1075-1076, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37474817
10.
11.
Proc Natl Acad Sci U S A ; 119(10): e2123363119, 2022 03 08.
Artículo en Inglés | MEDLINE | ID: mdl-35235450

RESUMEN

During mitosis, from late prophase onward, sister chromatids are connected along their entire lengths by axis-linking chromatin/structure bridges. During prometaphase/metaphase, these bridges ensure that sister chromatids retain a parallel, paranemic relationship, without helical coiling, as they undergo compaction. Bridges must then be removed during anaphase. Motivated by these findings, the present study has further investigated the process of anaphase sister separation. Morphological and functional analyses of mammalian mitoses reveal a three-stage pathway in which interaxis bridges play a prominent role. First, sister chromatid axes globally separate in parallel along their lengths, with concomitant bridge elongation, due to intersister chromatin pushing forces. Sister chromatids then peel apart progressively from a centromere to telomere region(s), step-by-step. During this stage, poleward spindle forces dramatically elongate centromere-proximal bridges, which are then removed by a topoisomerase IIα­dependent step. Finally, in telomere regions, widely separated chromatids remain invisibly linked, presumably by catenation, with final separation during anaphase B. During this stage increased separation of poles and/or chromatin compaction appear to be the driving force(s). Cohesin cleavage licenses these events, likely by allowing bridges to respond to imposed forces. We propose that bridges are not simply removed during anaphase but, in addition, play an active role in ensuring smooth and synchronous microtubule-mediated sister separation. Bridges would thereby be the topological gatekeepers of sister chromatid relationships throughout all stages of mitosis.


Asunto(s)
Anafase , Cromátides , Intercambio de Cromátides Hermanas , Proteínas de Ciclo Celular/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , ADN-Topoisomerasas de Tipo II/metabolismo , Humanos , Cohesinas
12.
Front Cell Dev Biol ; 9: 687132, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34900979

RESUMEN

Chromosome movement is prominent at mid-meiotic prophase and is proposed to enhance the efficiency and/or stringency of homolog pairing and/or to help prevent or resolve topological entanglements. Here, we combine fluorescent repressor operator system (FROS) labeling with three-dimensional (3D) live-cell imaging at high spatio-temporal resolution to define the detailed kinetics of mid-meiotic prophase motion for a single telomere-proximal locus in budding yeast. Telomere motions can be grouped into three general categories: (i) pauses, in which the telomere "jiggles in place"; (ii) rapid, straight/curvilinear motion which reflects Myo2/actin-mediated transport of the monitored telomere; and (iii) slower directional motions, most of which likely reflect indirectly promoted motion of the monitored telomere in coordination with actin-mediated motion of an unmarked telomere. These and other findings highlight the importance of dynamic assembly/disassembly of telomere/LINC/actin ensembles and also suggest important roles for nuclear envelope deformations promoted by actin-mediated telomere/LINC movement. The presented low-SNR (signal-to-noise ratio) imaging methodology provides opportunities for future exploration of homolog pairing and related phenomena.

13.
Curr Biol ; 31(21): 4713-4726.e4, 2021 11 08.
Artículo en Inglés | MEDLINE | ID: mdl-34480856

RESUMEN

Polyploidy is a major driver of evolutionary change. Autopolyploids, which arise by within-species whole-genome duplication, carry multiple nearly identical copies of each chromosome. This presents an existential challenge to sexual reproduction. Meiotic chromosome segregation requires formation of DNA crossovers (COs) between two homologous chromosomes. How can this outcome be achieved when more than two essentially equivalent partners are available? We addressed this question by comparing diploid, neo-autotetraploid, and established autotetraploid Arabidopsis arenosa using new approaches for analysis of meiotic CO patterns in polyploids. We discover that crossover interference, the classical process responsible for patterning of COs in diploid meiosis, is defective in the neo-autotetraploid but robust in the established autotetraploid. The presented findings suggest that, initially, diploid-like interference fails to act effectively on multivalent pairing and accompanying pre-CO recombination interactions and that stable autopolyploid meiosis can emerge by evolution of a "supercharged" interference process, which can now act effectively on such configurations. Thus, the basic interference mechanism responsible for simplifying CO patterns along chromosomes in diploid meiosis has evolved the capability to also simplify CO patterns among chromosomes in autopolyploids, thereby promoting bivalent formation. We further show that evolution of stable autotetraploidy preadapts meiosis to higher ploidy, which in turn has interesting mechanistic and evolutionary implications.


Asunto(s)
Arabidopsis , Arabidopsis/genética , Segregación Cromosómica/genética , Diploidia , Meiosis/genética , Poliploidía
14.
ACS Nano ; 15(3): 4115-4133, 2021 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-33596042

RESUMEN

Mechanoluminescent materials, which emit light in response to elastic deformation, are demanded for use as in situ stress sensors. ZnS doped with Mn is known to exhibit one of the lowest reported thresholds for appearance of mechanoluminescence, with repeatable light emission under contact pressure <10 MPa. The physical basis for such behavior remains as yet unclear. Here, reliable microscopic detection of mechanoluminescence of single ZnS:Mn microparticles, in combination with nanoscale structural characterization, provides evidence that the mechanoluminescent properties of these particles result from interplay between a non-centrosymmetric crystal lattice and its defects, viz., dislocations and stacking faults. Statistical analysis of the distributions of mechanoluminescence energy release trajectories reveals two distinct mechanisms of excitation: one attributable to a piezo-phototronic effect and the other due to dislocation motion. At pressures below 8.1 MPa, both mechanisms contribute to mechanoluminescent output, with a dominant contribution from the piezo-phototronic mechanism. In contrast, above 8.1 MPa, dislocation motion is the primary excitation source. For the piezo-phototronic mechanism, we propose a specific model that accounts for elastic ZnS:Mn mechanoluminescence under very low pressure. The charged interfaces in stacking faults lead to the presence of filled traps, which otherwise would be empty in the absence of the built-in electric field. Upon application of external stress, local enhancement of the piezoelectric field at the stacking faults' interfaces facilitates release of the trapped carriers and subsequent luminescence. This field enhancement explains how <10 MPa pressure produces thousands of photons.

15.
Proc Natl Acad Sci U S A ; 117(43): 26749-26755, 2020 10 27.
Artículo en Inglés | MEDLINE | ID: mdl-33051295

RESUMEN

Spatial patterns are ubiquitous in both physical and biological systems. We have recently discovered that mitotic chromosomes sequentially acquire two interesting morphological patterns along their structural axes [L. Chu et al., Mol. Cell, 10.1016/j.molcel.2020.07.002 (2020)]. First, axes of closely conjoined sister chromosomes acquire regular undulations comprising nearly planar arrays of sequential half-helices of similar size and alternating handedness, accompanied by periodic kinks. This pattern, which persists through all later stages, provides a case of the geometric form known as a "perversion." Next, as sister chromosomes become distinct parallel units, their individual axes become linked by bridges, which are themselves miniature axes. These bridges are dramatically evenly spaced. Together, these effects comprise a unique instance of spatial patterning in a subcellular biological system. We present evidence that axis undulations and bridge arrays arise by a single continuous mechanically promoted progression, driven by stress within the chromosome axes. We further suggest that, after sister individualization, this same stress also promotes chromosome compaction by rendering the axes susceptible to the requisite molecular remodeling. Thus, by this scenario, the continuous presence of mechanical stress within the chromosome axes could potentially underlie the entire morphogenetic chromosomal program. Direct analogies with meiotic chromosomes suggest that the same effects could underlie interactions between homologous chromosomes as required for gametogenesis. Possible mechanical bases for generation of axis stress and resultant deformations are discussed. Together, these findings provide a perspective on the macroscopic changes of organized chromosomes.


Asunto(s)
Cromatina/química , Cromosomas/química , Mitosis/genética , Morfogénesis/genética , Línea Celular , Cromátides/química , Cromátides/genética , Cromátides/metabolismo , Cromatina/genética , Cromatina/metabolismo , Cromosomas/genética , Cromosomas/metabolismo , Humanos
16.
Mol Cell ; 79(6): 902-916.e6, 2020 09 17.
Artículo en Inglés | MEDLINE | ID: mdl-32768407

RESUMEN

A long-standing conundrum is how mitotic chromosomes can compact, as required for clean separation to daughter cells, while maintaining close parallel alignment of sister chromatids. Pursuit of this question, by high resolution 3D fluorescence imaging of living and fixed mammalian cells, has led to three discoveries. First, we show that the structural axes of separated sister chromatids are linked by evenly spaced "mini-axis" bridges. Second, when chromosomes first emerge as discrete units, at prophase, they are organized as co-oriented sister linear loop arrays emanating from a conjoined axis. We show that this same basic organization persists throughout mitosis, without helical coiling. Third, from prophase onward, chromosomes are deformed into sequential arrays of half-helical segments of alternating handedness (perversions), accompanied by correlated kinks. These arrays fluctuate dynamically over <15 s timescales. Together these discoveries redefine the foundation for thinking about the evolution of mitotic chromosomes as they prepare for anaphase segregation.


Asunto(s)
Proteínas de Ciclo Celular/genética , Cromosomas/genética , Proteínas de Unión al ADN/genética , Mitosis/genética , Adenosina Trifosfatasas/genética , Anafase/genética , Animales , Proteínas de Ciclo Celular/aislamiento & purificación , Cromátides/genética , Proteínas Cromosómicas no Histona , ADN-Topoisomerasas de Tipo II/genética , Proteínas de Unión al ADN/aislamiento & purificación , Imagenología Tridimensional , Mamíferos , Metafase/genética , Profase/genética
17.
Nat Microbiol ; 5(8): 995-1001, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32424336

RESUMEN

Growth laws emerging from studies of cell populations provide essential constraints on the global mechanisms that coordinate cell growth1-3. The foundation of bacterial cell cycle studies relies on two interconnected dogmas that were proposed more than 50 years ago-the Schaechter-Maaloe-Kjeldgaard growth law that relates cell mass to growth rate1 and Donachie's hypothesis of a growth-rate-independent initiation mass4. These dogmas spurred many efforts to understand their molecular bases and physiological consequences5-14. Although they are generally accepted in the fast-growth regime, that is, for doubling times below 1 h, extension of these dogmas to the slow-growth regime has not been consistently achieved. Here, through a quantitative physiological study of Escherichia coli cell cycles over an extensive range of growth rates, we report that neither dogma holds in either the slow- or fast-growth regime. In their stead, linear relations between the cell mass and the rate of chromosome replication-segregation were found across the range of growth rates. These relations led us to propose an integral-threshold model in which the cell cycle is controlled by a licensing process, the rate of which is related in a simple way to chromosomal dynamics. These results provide a quantitative basis for predictive understanding of cell growth-cell cycle relationships.


Asunto(s)
Ciclo Celular , División Celular , Escherichia coli/metabolismo , Segregación Cromosómica , Cromosomas Bacterianos/genética , Medios de Cultivo/química , Replicación del ADN , Proteínas de Escherichia coli , Proteómica
18.
Nucleic Acids Res ; 47(22): 11691-11708, 2019 12 16.
Artículo en Inglés | MEDLINE | ID: mdl-31617566

RESUMEN

We have explored the meiotic roles of cohesin modulators Pds5 and Rad61/Wapl, in relation to one another, and to meiotic kleisin Rec8, for homolog pairing, all physically definable steps of recombination, prophase axis length and S-phase progression, in budding yeast. We show that Pds5 promotes early steps of recombination and thus homolog pairing, and also modulates axis length, with both effects independent of a sister chromatid. [Pds5+Rec8] promotes double-strand break formation, maintains homolog bias for crossover formation and promotes S-phase progression. Oppositely, the unique role of Rad61/Wapl is to promote non-crossover recombination by releasing [Pds5+Rec8]. For this effect, Rad61/Wapl probably acts to maintain homolog bias by preventing channeling into sister interactions. Mysteriously, each analyzed molecule has one role that involves neither of the other two. Overall, the presented findings suggest that Pds5's role in maintenance of sister chromatid cohesion during the mitotic prophase-analogous stage of G2/M is repurposed during meiosis prophase to promote interactions between homologs.


Asunto(s)
Proteínas de Ciclo Celular/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , Emparejamiento Cromosómico , Meiosis , Recombinación Genética/fisiología , Fase S/fisiología , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Ciclo Celular/genética , Células Cultivadas , Proteínas Cromosómicas no Histona/genética , Emparejamiento Cromosómico/genética , Segregación Cromosómica , Cromosomas Fúngicos , Meiosis/genética , Organismos Modificados Genéticamente , Unión Proteica , Fase S/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Intercambio de Cromátides Hermanas/genética
19.
Bioessays ; 41(10): e1800221, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31424607

RESUMEN

A striking feature of human female sexual reproduction is the high level of gametes that exhibit an aberrant number of chromosomes (aneuploidy). A high baseline observed in women of prime reproductive age is followed by a dramatic increase in older women. Proper chromosome segregation requires one or more DNA crossovers (COs) between homologous maternal and paternal chromosomes, in combination with cohesion between sister chromatid arms. In human females, CO designations occur normally, according to the dictates of CO interference, giving early CO-fated intermediates. However, ≈25% of these intermediates fail to mature to final CO products. This effect explains the high baseline of aneuploidy and is predicted to synergize with age-dependent cohesion loss to explain the maternal age effect. Here, modern advances in the understanding of crossing over and CO interference are reviewed, the implications of human female CO maturation inefficiency are further discussed, and areas of interest for future studies are suggested.


Asunto(s)
Aneuploidia , Cromosomas Humanos , Factores de Edad , Segregación Cromosómica , Femenino , Humanos , Masculino , Meiosis , Factores Sexuales
20.
Proc Natl Acad Sci U S A ; 116(25): 12400-12409, 2019 06 18.
Artículo en Inglés | MEDLINE | ID: mdl-31147459

RESUMEN

A central feature of meiosis is pairing of homologous chromosomes, which occurs in two stages: coalignment of axes followed by installation of the synaptonemal complex (SC). Concomitantly, recombination complexes reposition from on-axis association to the SC central region. We show here that, in the fungus Sordaria macrospora, this critical transition is mediated by robust interaxis bridges that contain an axis component (Spo76/Pds5), DNA, plus colocalizing Mer3/Msh4 recombination proteins and the Zip2-Zip4 mediator complex. Mer3-Msh4-Zip2-Zip4 colocalizing foci are first released from their tight axis association, dependent on the SC transverse-filament protein Sme4/Zip1, before moving to bridges and thus to a between-axis position. Ensuing shortening of bridges and accompanying juxtaposition of axes to 100 nm enables installation of SC central elements at sites of between-axis Mer3-Msh4-Zip2-Zip4 complexes. We show also that the Zip2-Zip4 complex has an intrinsic affinity for chromosome axes at early leptotene, where it localizes independently of recombination, but is dependent on Mer3. Then, later, Zip2-Zip4 has an intrinsic affinity for the SC central element, where it ultimately localizes to sites of crossover complexes at the end of pachytene. These and other findings suggest that the fundamental role of Zip2-Zip4 is to mediate the recombination/structure interface at all post-double-strand break stages. We propose that Zip2-Zip4 directly mediates a molecular handoff of Mer3-Msh4 complexes, from association with axis components to association with SC central components, at the bridge stage, and then directly mediates central region installation during SC nucleation.


Asunto(s)
Recombinación Genética , Sordariales/genética , Cromosomas Fúngicos , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Genes Fúngicos , Complejo Sinaptonémico/metabolismo
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