scholarly journals The Synaptonemal Complex Central Region Modulates Crossover Pathways and Feedback Control of Meiotic Double-strand Break Formation

2020 ◽  
Author(s):  
Min-Su Lee ◽  
Mika T. Higashide ◽  
Hyungseok Choi ◽  
Ke Li ◽  
Soogil Hong ◽  
...  
Keyword(s):  
Synaptonemal Complex ◽  
Central Region ◽  
Genetic Recombination ◽  
Strand Break ◽  
Late Prophase ◽  
Interacting Protein ◽  
Recombination Proteins ◽  
Central Regions ◽  
Chromosome Iii ◽  
Double Holliday Junction

SummaryThe synaptonemal complex (SC) is a proteinaceous structure that mediates homolog engagement and genetic recombination during meiosis. Zip-Mer-Msh (ZMM) proteins promote crossover (CO) formation and initiate SC formation. In SC elongation, the SUMOylated SC component Ecm11 and its interacting protein Gmc2 facilitate the polymerization of Zip1, a SC-central region component in budding yeast. Through physical recombination, cytological, and genetic analyses, we here demonstrate that ecm11 and gmc2 mutants exhibit chromosome-specific defects in meiotic recombination. CO frequencies were reduced on a short chromosome (chromosome III), whereas CO and non-crossover (NCO) frequencies were increased on a long chromosome (chromosome VII). Further, persistent double-strand breaks (DSBs) occurred in unsynapsed chromosome regions during the late prophase, suggesting the presence of a negative regulation of DSB formation. The Ecm11-Gmc2 (EG) complex could participate in joint molecule (JM) processing and/or double-Holliday junction resolution for CO-designated recombination of the ZMM-dependent pathway. However, absence of the EG complex ameliorated the JM-processing defect in zmm mutants, suggesting a role of these proteins in suppression of ZMM-independent recombination. Therefore, the EG complex fosters ZMM-dependent processing and resolution of JMs while suppressing ZMM-independent JM processing and late DSB formation. Hence, EG-mediated SC central regions, which display properties similar to those of liquid crystals, may function as a compartment for sequestering recombination proteins in and out of the process to ensure meiosis specificity during recombination.

Synaptonemal complexes of triploid (ZZW) chickens: Z–Z pairing predominates over Z–W pairing

Genome ◽  
1991 ◽  
Vol 34 (5) ◽  
pp. 718-726 ◽  
Author(s):  
Alberto J. Solari ◽  
M. H. Thorne ◽  
B. L. Sheldon ◽  
C. B. Gillies
Keyword(s):  
Synaptonemal Complex ◽  
Central Region ◽  
Sex Chromosomes ◽  
W Chromosome ◽  
Synaptonemal Complexes ◽  
Early Pachytene ◽  
Recombination Nodule ◽  
Recombination Nodules ◽  
Central Regions ◽  
Partial Elimination

Twelve triploid, ZZW chickens of ages ranging from day 19 of incubation to 15 days after hatching were used for oocyte analysis. Oocytes show 117 axes per nucleus. At early pachytene, most axes form double synaptonemal complexes (triplets). An average of 27 triplets, 12 bivalents, and 12 univalents was observed. Later, a partial elimination of triplets occurs, as they are converted into typical trivalents or bivalents and univalents. The number of recombination nodules per nucleus (52.7) is similar to that of diploids. These nodules can occur in register in both central regions of a triplet (no lateral interference), and they probably stabilize the central region. Among 31 oocytes, 29 had a regular ZZ bivalent and a W univalent, and only 2 had triple pairing between a ZZ bivalent and a terminal region of the W axis (less than 1 μm in length and having a terminal recombination nodule). Competition for pairing between the gonosomes results in a large (93.5% of cases) predominance of Z–Z pairing, because of a relatively minor homology between the W and Z chromosomes. The prevailing pairing failure of the W chromosome may lead to early oocyte loss.Key words: sex chromosomes, triploids, synaptonemal complex, Z–W pairing, chicken, recombination nodules.

scholarly journals Polo-like kinase-dependent phosphorylation of the synaptonemal complex protein SYP-4 regulates double-strand break formation through a negative feedback loop.

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Saravanapriah Nadarajan ◽  
Talley J Lambert ◽  
Elisabeth Altendorfer ◽  
Jinmin Gao ◽  
Michael D Blower ◽  
...  
Keyword(s):  
Synaptonemal Complex ◽  
Central Region ◽  
Feedback Loop ◽  
Strand Break ◽  
Dynamic State ◽  
Strand Breaks ◽  
Homologous Chromosomes ◽  
C Elegans ◽  
Complex Protein ◽  
Synaptonemal Complex Protein

The synaptonemal complex (SC) is an ultrastructurally conserved proteinaceous structure that holds homologous chromosomes together and is required for the stabilization of pairing interactions and the completion of crossover (CO) formation between homologs during meiosis I. Here, we identify a novel role for a central region component of the SC, SYP-4, in negatively regulating formation of recombination-initiating double-strand breaks (DSBs) via a feedback loop triggered by crossover designation in C. elegans. We found that SYP-4 is phosphorylated dependent on Polo-like kinases PLK-1/2. SYP-4 phosphorylation depends on DSB formation and crossover designation, is required for stabilizing the SC in pachytene by switching the central region of the SC from a more dynamic to a less dynamic state, and negatively regulates DSB formation. We propose a model in which Polo-like kinases recognize crossover designation and phosphorylate SYP-4 thereby stabilizing the SC and making chromosomes less permissive for further DSB formation.

scholarly journals Building bridges to move recombination complexes

2019 ◽  
Vol 116 (25) ◽  
pp. 12400-12409 ◽  
Author(s):  
Emeline Dubois ◽  
Arnaud De Muyt ◽  
Jessica L. Soyer ◽  
Karine Budin ◽  
Mathieu Legras ◽  
...  
Keyword(s):  
Central Region ◽  
Central Element ◽  
Strand Break ◽  
Central Feature ◽  
Homologous Chromosomes ◽  
Recombination Proteins ◽  
Axis Position ◽  
Two Stages ◽  
Filament Protein

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.

scholarly journals Focused Genetic Recombination of Bacteriophage T4 Initiated by Double-Strand Breaks

Genetics ◽  
2002 ◽  
Vol 162 (2) ◽  
pp. 543-556
Author(s):  
Victor Shcherbakov ◽  
Igor Granovsky ◽  
Lidiya Plugina ◽  
Tamara Shcherbakova ◽  
Svetlana Sizova ◽  
...  
Keyword(s):  
Genetic Recombination ◽  
Bacteriophage T4 ◽  
Proximal Part ◽  
Coupling Model ◽  
Strand Break ◽  
Double Strand Breaks ◽  
Strand Breaks ◽  
The Right ◽  
Frequency Distance

Abstract A model system for studying double-strand-break (DSB)-induced genetic recombination in vivo based on the ets1 segCΔ strain of bacteriophage T4 was developed. The ets1, a 66-bp DNA fragment of phage T2L containing the cleavage site for the T4 SegC site-specific endonuclease, was inserted into the proximal part of the T4 rIIB gene. Under segC+ conditions, the ets1 behaves as a recombination hotspot. Crosses of the ets1 against rII markers located to the left and to the right of ets1 gave similar results, thus demonstrating the equal and symmetrical initiation of recombination by either part of the broken chromosome. Frequency/distance relationships were studied in a series of two- and three-factor crosses with other rIIB and rIIA mutants (all segC+) separated from ets1 by 12-2100 bp. The observed relationships were readily interpretable in terms of the modified splice/patch coupling model. The advantages of this localized or focused recombination over that distributed along the chromosome, as a model for studying the recombination-replication pathway in T4 in vivo, are discussed.

scholarly journals Human SIRT6 Promotes DNA End Resection Through CtIP Deacetylation

Science ◽  
2010 ◽  
Vol 329 (5997) ◽  
pp. 1348-1353 ◽  
Author(s):  
Abderrahmane Kaidi ◽  
Brian T. Weinert ◽  
Chunaram Choudhary ◽  
Stephen P. Jackson
Keyword(s):  
Homologous Recombination ◽  
Genome Stability ◽  
Protein A ◽  
Strand Break ◽  
Dsb Repair ◽  
Interacting Protein ◽  
Dna Double Strand Break ◽  
Dna End Resection ◽  
Lysine Deacetylases ◽  
End Resection

SIRT6 belongs to the sirtuin family of protein lysine deacetylases, which regulate aging and genome stability. We found that human SIRT6 has a role in promoting DNA end resection, a crucial step in DNA double-strand break (DSB) repair by homologous recombination. SIRT6 depletion impaired the accumulation of replication protein A and single-stranded DNA at DNA damage sites, reduced rates of homologous recombination, and sensitized cells to DSB-inducing agents. We identified the DSB resection protein CtIP [C-terminal binding protein (CtBP) interacting protein] as a SIRT6 interaction partner and showed that SIRT6-dependent CtIP deacetylation promotes resection. A nonacetylatable CtIP mutant alleviated the effect of SIRT6 depletion on resection, thus identifying CtIP as a key substrate by which SIRT6 facilitates DSB processing and homologous recombination. These findings further clarify how SIRT6 promotes genome stability.

scholarly journals Low dust emissivities and radial variations in the envelopes of Class 0 protostars: possible signature of early grain growth

2019 ◽  
Vol 632 ◽  
pp. A5 ◽  
Author(s):  
M. Galametz ◽  
A. J. Maury ◽  
V. Valdivia ◽  
L. Testi ◽  
A. Belloche ◽  
...  
Keyword(s):  
Grain Size ◽  
Star Formation ◽  
Grain Growth ◽  
Central Region ◽  
Radial Gradient ◽  
Central Regions ◽  
Dust Composition ◽  
Dust Grain ◽  
Early Phases ◽  
Inner Envelope

Context. Analyzing the properties of dust and its evolution in the early phases of star formation is crucial to put constraints on the collapse and accretion processes as well as on the pristine properties of planet-forming seeds. Aims. In this paper, we aim to investigate the variations of the dust grain size in the envelopes of the youngest protostars. Methods. We analyzed Plateau de Bure interferometric observations at 1.3 and 3.2 mm for 12 Class 0 protostars obtained as part of the CALYPSO survey. We performed our analysis in the visibility domain and derived dust emissivity index (β1−3mm) profiles as a function of the envelope radius at 200–2000 au scales. Results. Most of the protostellar envelopes show low dust emissivity indices decreasing toward the central regions. The decreasing trend remains after correction of the (potentially optically thick) central region emission, with surprisingly low β1−3mm < 1 values across most of the envelope radii of NGC 1333-IRAS 4A, NGC 1333-IRAS 4B, SVS13B, and Serpens-SMM4. Conclusions. We discuss the various processes that could explain such low and varying dust emissivity indices at envelope radii 200–2000 au. Our observations of extremely low dust emissivity indices could trace the presence of large (millimeter-size) grains in Class 0 envelopes, in which case our results would point to a radial increase of the dust grain size toward the inner envelope regions. While it is expected that large grains in young protostellar envelopes could be built via grain growth and coagulation, we stress that the typical timescales required to build millimeter grains in current coagulation models are at odds with the youth of our Class 0 protostars. Additional variations in the dust composition could also partly contribute to the low β1−3mm we observe. We find that the steepness of the β1−3mm radial gradient depends strongly on the envelope mass, which might favor a scenario in which large grains are built in high-density protostellar disks and transported to the intermediate envelope radii, for example with the help of outflows and winds.

scholarly journals Alteration of genetic recombination and double-strand break repair in human cells by progerin expression

DNA Repair ◽  
2020 ◽  
Vol 96 ◽  
pp. 102975 ◽  
Author(s):  
Celina J. Komari ◽  
Anne O. Guttman ◽  
Shelby R. Carr ◽  
Taylor L. Trachtenberg ◽  
Elise A. Orloff ◽  
...  
Keyword(s):  
Genetic Recombination ◽  
Strand Break ◽  
Double Strand Break ◽  
Human Cells ◽  
Double Strand Break Repair ◽  
Break Repair
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