scholarly journals Identification of a meiosis-specific chromosome movement pattern induced by persistent DNA damage

2020 ◽  
Author(s):  
Daniel León-Periñán ◽  
Alfonso Fernández-Álvarez

ABSTRACTAs one of the main events occurring during meiotic prophase, the dynamics of meiotic chromosome movement is not yet well understood. Currently, although it is well-established that chromosome movement takes an important role during meiotic recombination promoting the pairing between homologous chromosomes and avoiding excessive chromosome associations, it is mostly unclear whether those movements follow a particular fixed pattern, or are stochastically distributed. Using Schizosaccharomyces pombe as a model organism, which exhibits dramatic meiotic nuclear oscillations, we have developed a computationally automatized statistical analysis of three-dimensional time-lapse fluorescence information in order to characterize nuclear trajectories and morphological patterns during meiotic prophase. This approach allowed us to identify a patterned oscillatory microvariation during the meiotic nuclear motion. Additionally, we showed evidence suggesting that this unexpected oscillatory motif might be due to the detection of persistent DNA damage during the nuclear movement, supporting how the nucleus also regulates its oscillations. Our computationally automatized tool will be useful for the identification of new patterns of nuclear oscillations during gametogenesis.

2020 ◽  
Author(s):  
Eric J.G. Pollitt ◽  
Oliver Carnell ◽  
Egbert Hoiczyk ◽  
Jeffrey Green

AbstractMycobacterium smegmatis spreads over soft agar surfaces by sliding motility, a form of passive motility in which growth and reduction of surface adhesion enable the bacteria to push each other outwards. Hence, sliding motility is mostly associated with round colonies. However, M. smegmatis sliding colonies can also produce long, pointed dendrites. Round sliding colonies were readily reproduced, but our non-round colonies were different from those seen previously. The latter (named digitate colonies) had centimetre-long linear protrusions, containing a central channel filled with a free-flowing suspension of M. smegmatis and solid aggregates. Digitate colonies had both a surface pellicle and an inner biofilm component surrounding a central channel, which sat in a cleft in the agar. Time-lapse microscopy showed that the expansion of the fluid-filled channel enabled the lengthwise extension of the protrusions without any perceptible growth of the bacteria taking place. These observations represent a novel type of sliding motility, named hydraulic sliding, associated with a specialised colony structure and the apparent generation of force by expansion of a liquid core. As this structure requires pellicle formation without an initial liquid culture it implies the presence of an unstudied mycobacterial behaviour that may be important for colonisation and virulence.Originality-Significance StatementThis study is the first to identify a new form of passive motility in the mycobacteria; hydraulic sliding, in which liquid expansion is the cause of motility. This form of motility has so far never been described in bacteria. The study also reveals new ways mycobacteria can form biofilms and colonize complex three-dimensional substrates, aspects of mycobacterial biology that are important for infection, pathogenesis and vaccine development.Author SummaryMycobacterium smegmatis is used as a non-pathogenic model organism for pathogenic mycobacteria. During growth, M. smegmatis can move passively over soft agar surfaces by a process called sliding motility, whereby colony growth directly pushes cells outwards. Although passive, sliding motility is believed to be important in allowing bacteria to colonise surfaces. Sliding motility however does not fully account for how M. smegmatis produces dendritic colonies. We attempted to generate dendritic colonies but found instead that the cells produced colonies that had larger protrusions radiating from them (digitate colonies). Digitate colonies are a previously unobserved phenomenon, in that the bacteria create a biofilm-lined, fluid-filled, pellicle-covered, deep cleft in the agar and move across the surface by the expansion of the contained liquid core of the protrusions. Given the new structure and the new mechanism of expansion we have termed this set of behaviours hydraulic sliding. These observations are important as it is a new variation in the way bacteria can move, generate biofilms (notably mycobacterial pellicle) and colonize complex three-dimensional substrates.


Author(s):  
Sara González-Arranz ◽  
Jennifer M. Gardner ◽  
Zulin Yu ◽  
Neem J. Patel ◽  
Jonna Heldrich ◽  
...  

ABSTRACTThe H2A.Z histone variant is deposited into chromatin by the SWR1 complex affecting multiple aspects of meiosis. Here we describe a SWR1-independent localization of H2A.Z at meiotic telomeres and the centrosome. We demonstrate that H2A.Z colocalizes and interacts with Mps3, the SUN component of the LINC complex that spans the nuclear envelope and links meiotic telomeres to the cytoskeleton promoting meiotic chromosome movement. H2A.Z also interacts with the meiosis-specific Ndj1 protein that anchors telomeres to the nuclear periphery via Mps3. Telomeric localization of H2A.Z depends on Ndj1 and the N-terminal domain of Mps3. Although telomeric attachment to the nuclear envelope is maintained in the absence of H2A.Z, the distribution of Mps3 is altered. The velocity of chromosome movement during meiotic prophase I is reduced in the htz1Δ mutant lacking H2A.Z, but it is unaffected in swr1Δ cells. We reveal that H2A.Z is an additional LINC-associated factor that contributes to promote telomere-driven chromosome motion critical for error-free gametogenesis.


2017 ◽  
Vol 36 (5) ◽  
pp. 519-528 ◽  
Author(s):  
Tomoyo Tanaka ◽  
Mitsuhiro Hoshijima ◽  
Junko Sunaga ◽  
Takashi Nishida ◽  
Mana Hashimoto ◽  
...  

2013 ◽  
Vol 33 (16) ◽  
pp. 3286-3298 ◽  
Author(s):  
Zhongqi Ge ◽  
Devi Nair ◽  
Xiaoyan Guan ◽  
Neha Rastogi ◽  
Michael A. Freitas ◽  
...  

The best-characterized acetylation of newly synthesized histone H4 is the diacetylation of the NH2-terminal tail on lysines 5 and 12. Despite its evolutionary conservation, this pattern of modification has not been shown to be essential for either viability or chromatin assembly in any model organism. We demonstrate that mutations in histone H4 lysines 5 and 12 in yeast confer hypersensitivity to replication stress and DNA-damaging agents when combined with mutations in histone H4 lysine 91, which has also been found to be a site of acetylation on soluble histone H4. In addition, these mutations confer a dramatic decrease in cell viability when combined with mutations in histone H3 lysine 56. We also show that mutation of the sites of acetylation on newly synthesized histone H4 results in defects in the reassembly of chromatin structure that accompanies the repair of HO-mediated double-strand breaks. This defect is not due to a decrease in the level of histone H3 lysine 56 acetylation. Intriguingly, mutations that alter the sites of newly synthesized histone H4 acetylation display a marked decrease in levels of phosphorylated H2A (γ-H2AX) in chromatin surrounding the double-strand break. These results indicate that the sites of acetylation on newly synthesized histones H3 and H4 can function in nonoverlapping ways that are required for chromatin assembly, viability, and DNA damage response signaling.


2021 ◽  
Vol 7 (3) ◽  
pp. eabe3882
Author(s):  
Jenny F. Nathans ◽  
James A. Cornwell ◽  
Marwa M. Afifi ◽  
Debasish Paul ◽  
Steven D. Cappell

The G1-S checkpoint is thought to prevent cells with damaged DNA from entering S phase and replicating their DNA and efficiently arrests cells at the G1-S transition. Here, using time-lapse imaging and single-cell tracking, we instead find that DNA damage leads to highly variable and divergent fate outcomes. Contrary to the textbook model that cells arrest at the G1-S transition, cells triggering the DNA damage checkpoint in G1 phase route back to quiescence, and this cellular rerouting can be initiated at any point in G1 phase. Furthermore, we find that most of the cells receiving damage in G1 phase actually fail to arrest and proceed through the G1-S transition due to persistent cyclin-dependent kinase (CDK) activity in the interval between DNA damage and induction of the CDK inhibitor p21. These observations necessitate a revised model of DNA damage response in G1 phase and indicate that cells have a G1 checkpoint.


2006 ◽  
Vol 173 (1) ◽  
pp. 27-33 ◽  
Author(s):  
Takamune T. Saito ◽  
Daisuke Okuzaki ◽  
Hiroshi Nojima

During meiotic prophase I of the fission yeast Schizosaccharomyces pombe, oscillatory nuclear movement occurs. This promotes homologous chromosome pairing and recombination and involves cortical dynein, which plays a pivotal role by generating a pulling force with the help of an unknown dynein anchor. We show that Mcp5, the homologue of the budding yeast dynein anchor Num1, may be this putative dynein anchor. mcp5+ is predominantly expressed during meiotic prophase, and GFP-Mcp5 localizes at the cell cortex. Moreover, the mcp5Δ strain lacks the oscillatory nuclear movement. Accordingly, homologous pairing and recombination rates of the mcp5Δ strain are significantly reduced. Furthermore, the cortical localization of dynein heavy chain 1 appears to be reduced in mcp5Δ cells. Finally, the full function of Mcp5 requires its coiled-coil and pleckstrin homology (PH) domains. Our results suggest that Mcp5 localizes at the cell cortex through its PH domain and functions as a dynein anchor, thereby facilitating nuclear oscillation.


2018 ◽  
Vol 2 (4) ◽  
pp. 76 ◽  
Author(s):  
Kai Oßwald ◽  
Ingo Lochmahr ◽  
Yasin Bagci ◽  
Peter Saile

Hand scraping is a manual surface finishing process that, despite its low productivity and high cost, is still applied in many industries because of its advantages concerning accuracy and tribology. In the presented microanalysis forces, movement patterns and tool orientation of individual hand scraping strokes were measured using a test stand, specifically designed for this purpose. It utilizes a camera, a three dimensional dynamometer, and an inertial measurement unit (IMU). The results show the basic characteristics of hand scraping. Typical courses of relevant quantities like cutting force, passive force, clearance, and directional angle are shown. In addition, the movement pattern of the tool during individual scraping strokes is analyzed. This research aims to contribute to a later implementation of automated scraping. The conducted research creates a base for future research regarding different scraping methods and achieved results.


2019 ◽  
Vol 37 (5) ◽  
pp. 469-481 ◽  
Author(s):  
Visweswara C. Gudla ◽  
Alistair Garner ◽  
Malte Storm ◽  
Parmesh Gajjar ◽  
James Carr ◽  
...  

AbstractEnvironmentally induced cracking (EIC) in a sensitized high-strength AA5083 H131 alloy has been investigated using time-lapse synchrotron X-ray computed tomography combined with post-mortem correlative characterization. Small corrosion features deliberately introduced in a pre-exposure step were found to be the site of initiation for over 95% of the 44 EIC cracks that developed under slow strain rate testing. Detailed analysis using three-dimensional electron backscatter diffraction and energy-dispersive spectroscopy analysis of a single crack confirmed the intergranular nature of the cracks from the start and that the pre-exposure corrosion was associated with an α-AlFeMnSi particle cluster. It also appears that several cracks may have initiated at this site, which later coalesced to form the 300-μm-long crack that ultimately developed. Of further note is the fact that initiation of the EIC cracks across the sample started below the yield strength and continued beyond the ultimate tensile strength. The most rapid crack propagation occurred during sample extension following a period of fixed displacement.


2017 ◽  
Vol 216 (2) ◽  
pp. 393-408 ◽  
Author(s):  
Benjamin Alleva ◽  
Nathan Balukoff ◽  
Amy Peiper ◽  
Sarit Smolikove

In meiotic prophase I, homologous chromosome pairing is promoted through chromosome movement mediated by nuclear envelope proteins, microtubules, and dynein. After proper homologue pairing has been established, the synaptonemal complex (SC) assembles along the paired homologues, stabilizing their interaction and allowing for crossing over to occur. Previous studies have shown that perturbing chromosome movement leads to pairing defects and SC polycomplex formation. We show that FKB-6 plays a role in SC assembly and is required for timely pairing and proper double-strand break repair kinetics. FKB-6 localizes outside the nucleus, and in its absence, the microtubule network is altered. FKB-6 is required for proper movement of dynein, increasing resting time between movements. Attenuating chromosomal movement in fkb-6 mutants partially restores the defects in synapsis, in agreement with FKB-6 acting by decreasing chromosomal movement. Therefore, we suggest that FKB-6 plays a role in regulating dynein movement by preventing excess chromosome movement, which is essential for proper SC assembly and homologous chromosome pairing.


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