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Jan-willem Veening - One of the best experts on this subject based on the ideXlab platform.
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Tracking of Chromosome dynamics in live Streptococcus pneumoniae reveals that transcription promotes Chromosome Segregation.
Molecular microbiology, 2014Co-Authors: Morten Kjos, Jan-willem VeeningAbstract:Chromosome Segregation is an essential part of the bacterial cell cycle but is poorly characterized in oval-shaped streptococci. Using time-lapse fluorescence microscopy and total internal reflection fluorescence microscopy, we have tracked the dynamics of Chromosome Segregation in live cells of the human pathogen Streptococcus pneumoniae. Our observations show that the Chromosome Segregation process last for two-thirds of the total cell cycle; the origin region segregates rapidly in the early stages of the cell cycle while nucleoid Segregation finishes just before cell division. Previously we have demonstrated that the DNA-binding protein ParB and the condensin SMC promote efficient Chromosome Segregation, likely by an active mechanism. We now show that in the absence of SMC, cell division can occur over the unsegregated Chromosomes. However, neither smc nor parB are essential in S. pneumoniae, suggesting the importance of additional mechanisms. Here we have identified the process of transcription as one of these mechanisms important for Chromosome Segregation in S. pneumoniae. Transcription inhibitors rifampicin and streptolydigin as well as mutants affected in transcription elongation cause Chromosome Segregation defects. Together, our results highlight the importance of passive (or indirect) processes such as transcription for Chromosome Segregation in oval-shaped bacteria.
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SMC is recruited to oriC by ParB and promotes Chromosome Segregation in Streptococcus pneumoniae.
Molecular microbiology, 2011Co-Authors: Anita Minnen, Laetitia Attaiech, Maria Thon, Stephan Gruber, Jan-willem VeeningAbstract:Segregation of replicated Chromosomes is an essential process in all organisms. How bacteria, such as the oval-shaped human pathogen Streptococcus pneumoniae, efficiently segregate their Chromosomes is poorly understood. Here we show that the pneumococcal homologue of the DNA-binding protein ParB recruits S. pneumoniae condensin (SMC) to centromere-like DNA sequences (parS) that are located near the origin of replication, in a similar fashion as was shown for the rod-shaped model bacterium Bacillus subtilis. In contrast to B. subtilis, smc is not essential in S. pneumoniae, and Δsmc cells do not show an increased sensitivity to gyrase inhibitors or high temperatures. However, deletion of smc and/or parB results in a mild Chromosome Segregation defect. Our results show that S. pneumoniae contains a functional Chromosome Segregation machine that promotes efficient Chromosome Segregation by recruitment of SMC via ParB. Intriguingly, the data indicate that other, as of yet unknown mechanisms, are at play to ensure proper Chromosome Segregation in this organism.
Phong T. Tran - One of the best experts on this subject based on the ideXlab platform.
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Fission yeast neddylation ligase Dcn1 facilitates cohesin cleavage and Chromosome Segregation at anaphase
Biology open, 2017Co-Authors: Lan Lin, Li Chen, Phong T. TranAbstract:Posttranslational protein modification such as phosphorylation and ubiquitination are critical during mitosis to ensure proper timing and progression of Chromosome Segregation. It has been recently recognized that another type of protein modification – neddylation – may also regulate mitosis and Chromosome Segregation. The conserved protein DCN1 (defective cullin neddylation 1) has been shown, when knock-downed by RNAi, to result in multinucleated cells and/or blockage of cell proliferation. However, how DCN1 functions in mitosis and Chromosome Segregation is not known. We report here the fission yeast dcn1 + and its role in mitosis and Chromosome Segregation. Dcn1-GFP localizes to the nucleus throughout the cell cycle. dcn1- deletion ( dcn1Δ ) leads to Chromosome and kinetochore lagging at anaphase, resulting from delayed and attenuated cohesin cleavage and sister chromatids separation. These results put Dcn1 upstream of the anaphase promoting complex/cyclosome APC/C pathway. We propose a mechanism for Dcn1 function at mitosis.
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csi2p modulates microtubule dynamics and organizes the bipolar spindle for Chromosome Segregation
Molecular biology of the cell, 2014Co-Authors: Judite Costa, V. Mohini Khare, Phong T. TranAbstract:Proper Chromosome Segregation is of paramount importance for proper genetic inheritance. Defects in Chromosome Segregation can lead to aneuploidy, which is a hallmark of cancer cells. Eukaryotic Chromosome Segregation is accomplished by the bipolar spindle. Additional mechanisms, such as the spindle assembly checkpoint and centromere positioning, further help to ensure complete Segregation fidelity. Here we present the fission yeast csi2+. csi2p localizes to the spindle poles, where it regulates mitotic microtubule dynamics, bipolar spindle formation, and subsequent Chromosome Segregation. csi2 deletion (csi2Δ) results in abnormally long mitotic microtubules, high rate of transient monopolar spindles, and subsequent high rate of Chromosome Segregation defects. Because csi2Δ has multiple phenotypes, it enables estimates of the relative contribution of the different mechanisms to the overall Chromosome Segregation process. Centromere positioning, microtubule dynamics, and bipolar spindle formation can all contribute to Chromosome Segregation. However, the major determinant of Chromosome Segregation defects in fission yeast may be microtubule dynamic defects.
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antagonistic spindle motors and maps regulate metaphase spindle length and Chromosome Segregation
Current Biology, 2013Co-Authors: Viktoriya Syrovatkina, Phong T. TranAbstract:Summary Metaphase describes a phase of mitosis where Chromosomes are attached and oriented on the bipolar spindle for subsequent Segregation at anaphase. In diverse cell types, the metaphase spindle is maintained at characteristic constant length [1–3]. Metaphase spindle length is proposed to be regulated by a balance of pushing and pulling forces generated by distinct sets of spindle microtubules (MTs) and their interactions with motors and MT-associated proteins (MAPs). Spindle length is further proposed to be important for Chromosome Segregation fidelity, as cells with shorter- or longer-than-normal metaphase spindles, generated through deletion or inhibition of individual mitotic motors or MAPs, showed Chromosome Segregation defects. To test the force-balance model of spindle length control and its effect on Chromosome Segregation, we applied fast microfluidic temperature control with live-cell imaging to monitor the effect of deleting or switching off different combinations of antagonistic force contributors in the fission yeast metaphase spindle. We show that the spindle midzone proteins kinesin-5 cut7p and MT bundler ase1p contribute to outward-pushing forces and that the spindle kinetochore proteins kinesin-8 klp5/6p and dam1p contribute to inward-pulling forces. Removing these proteins individually led to aberrant metaphase spindle length and Chromosome Segregation defects. Removing these proteins in antagonistic combination rescued the defective spindle length and in some combinations also partially rescued Chromosome Segregation defects.
Angelika Amon - One of the best experts on this subject based on the ideXlab platform.
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Chromosome Segregation fidelity in epithelia requires tissue architecture
Cell, 2018Co-Authors: Kristin A Knouse, Kristina E Lopez, Marc Bachofner, Angelika AmonAbstract:Much of our understanding of Chromosome Segregation is based on cell culture systems. Here, we examine the importance of the tissue environment for Chromosome Segregation by comparing Chromosome Segregation fidelity across several primary cell types in native and nonnative contexts. We discover that epithelial cells have increased Chromosome misSegregation outside of their native tissues. Using organoid culture systems, we show that tissue architecture, specifically integrin function, is required for accurate Chromosome Segregation. We find that tissue architecture enhances the correction of merotelic microtubule-kinetochore attachments, and this is especially important for maintaining Chromosome stability in the polyploid liver. We propose that disruption of tissue architecture could underlie the widespread Chromosome instability across epithelial cancers. Moreover, our findings highlight the extent to which extracellular context can influence intrinsic cellular processes and the limitations of cell culture systems for studying cells that naturally function within a tissue.
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role of polo like kinase cdc5 in programming meiosis i Chromosome Segregation
Science, 2003Co-Authors: Brian H Lee, Angelika AmonAbstract:Meiosis is a specialized cell division in which two Chromosome Segregation phases follow a single DNA replication phase. The budding yeast Polo-like kinase Cdc5 was found to be instrumental in establishing the meiosis I Chromosome Segregation program. Cdc5 was required to phosphorylate and remove meiotic cohesin from Chromosomes. Furthermore, in the absence of CDC5 kinetochores were bioriented during meiosis I, and Mam1, a protein essential for coorientation, failed to associate with kinetochores. Thus, sister-kinetochore coorientation and Chromosome Segregation during meiosis I are coupled through their dependence on CDC5.
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The Cdc14 Phosphatase and the FEAR Network Control Meiotic Spindle Disassembly and Chromosome Segregation
Developmental cell, 2003Co-Authors: Adele L. Marston, Brian H Lee, Angelika AmonAbstract:During meiosis, DNA replication is followed by two consecutive rounds of Chromosome Segregation. Cells lacking the protein phosphatase CDC14 or its regulators, SPO12 and SLK19, undergo only a single meiotic division, with some Chromosomes segregating reductionally and others equationally. We find that this abnormal Chromosome behavior is due to an uncoupling of meiotic events. Anaphase I spindle disassembly is delayed in cdc14-1, slk19Delta, or spo12Delta mutants, but the Chromosome Segregation cycle continues, so that both meiotic Chromosome Segregation phases take place on the persisting meiosis I spindle. Our results show that Cdc14, Slk19, and Spo12 are not only required for meiosis I spindle disassembly but also play a pivotal role in establishing two consecutive Chromosome Segregation phases, a key feature of the meiotic cell cycle.
Gary J. Gorbsky - One of the best experts on this subject based on the ideXlab platform.
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The Consequences of Chromosome Segregation Errors in Mitosis and Meiosis
Biology, 2017Co-Authors: Tamara A. Potapova, Gary J. GorbskyAbstract:Mistakes during cell division frequently generate changes in Chromosome content, producing aneuploid or polyploid progeny cells. Polyploid cells may then undergo abnormal division to generate aneuploid cells. Chromosome Segregation errors may also involve fragments of whole Chromosomes. A major consequence of Segregation defects is change in the relative dosage of products from genes located on the missegregated Chromosomes. Abnormal expression of transcriptional regulators can also impact genes on the properly segregated Chromosomes. The consequences of these perturbations in gene expression depend on the specific Chromosomes affected and on the interplay of the aneuploid phenotype with the environment. Most often, these novel Chromosome distributions are detrimental to the health and survival of the organism. However, in a changed environment, alterations in gene copy number may generate a more highly adapted phenotype. Chromosome Segregation errors also have important implications in human health. They may promote drug resistance in pathogenic microorganisms. In cancer cells, they are a source for genetic and phenotypic variability that may select for populations with increased malignance and resistance to therapy. Lastly, Chromosome Segregation errors during gamete formation in meiosis are a primary cause of human birth defects and infertility. This review describes the consequences of mitotic and meiotic errors focusing on novel concepts and human health.
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The spindle checkpoint and Chromosome Segregation in meiosis.
The FEBS journal, 2015Co-Authors: Gary J. GorbskyAbstract:The spindle checkpoint is a key regulator of Chromosome Segregation in mitosis and meiosis. Its function is to prevent precocious anaphase onset before Chromosomes have achieved bipolar attachment to the spindle. The spindle checkpoint comprises a complex set of signaling pathways that integrate microtubule dynamics, biomechanical forces at the kinetochores, and intricate regulation of protein interactions and post-translational modifications. Historically, many key observations that gave rise to the initial concepts of the spindle checkpoint were made in meiotic systems. In contrast with mitosis, the two distinct Chromosome Segregation events of meiosis present a special challenge for the regulation of checkpoint signaling. Preservation of fidelity in Chromosome Segregation in meiosis, controlled by the spindle checkpoint, also has a significant impact in human health. This review highlights the contributions from meiotic systems in understanding the spindle checkpoint as well as the role of checkpoint signaling in controlling the complex divisions of meiosis.
Jeff Errington - One of the best experts on this subject based on the ideXlab platform.
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Diversity and redundancy in bacterial Chromosome Segregation mechanisms
Philosophical transactions of the Royal Society of London. Series B Biological sciences, 2005Co-Authors: Jeff Errington, Heath MurrayAbstract:Bacterial cells are much smaller and have a much simpler overall structure and organization than eukaryotes. Several prominent differences in cell organization are relevant to the mechanisms of Chromosome Segregation, particularly the lack of an overt Chromosome condensation/decondensation cycle and the lack of a microtubule-based spindle. Although bacterial Chromosomes have a rather dispersed appearance, they nevertheless have an underlying high level of spatial organization. During the DNA replication cycle, early replicated (oriC) regions are localized towards the cell poles, whereas the late replicated terminus (terC) region is medially located. This spatial organization is thought to be driven by an active Segregation mechanism that separates the sister Chromosomes continuously as replication proceeds. Comparisons of various well-characterized bacteria suggest that the mechanisms of Chromosome Segregation are likely to be diverse, and that in many bacteria, multiple overlapping mechanisms may contribute to efficient Segregation. One system in which the molecular mechanisms of Chromosome Segregation are beginning to be elucidated is that of sporulating cells of Bacillus subtilis. The key components of this system have been identified, and their functions are understood, in outline. Although this system appears to be specialized, most of the functions are conserved widely throughout the bacteria.
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Septation and Chromosome Segregation during sporulation in Bacillus subtilis.
Current opinion in microbiology, 2001Co-Authors: Jeff ErringtonAbstract:The early stages of sporulation in Bacillus subtilis incorporate a modified, highly asymmetric cell division. It is now clear that most, if not all, of the components of the vegetative division machinery are used also for asymmetric division. However, the machinery for Chromosome Segregation may differ significantly between vegetative growth and sporulation. Several interesting checkpoint mechanisms couple cell cycle events to gene expression early in sporulation. This review summarises important advances in the understanding of Chromosome Segregation and cell division at the onset of sporulation in B.subtilis in the past three years.
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Upheaval in the bacterial nucleoid: an active Chromosome Segregation mechanism
Trends in genetics : TIG, 1999Co-Authors: Michaela Sharpe, Jeff ErringtonAbstract:Recent advances have completely overturned the classical view of Chromosome Segregation in bacteria. Far from being a passive process involving gradual separation of the Chromosomes, an active, possibly mitotic-like machinery is now known to exist. Soon after the initiation of DNA replication, the newly replicated copies of the oriC region, behaving rather like eukaryotic centromeres, move rapidly apart towards opposite poles of the cell. They then determine the positions that will be taken up by the newly formed sister nucleoids when DNA replication has been completed. Thus, the gradual expansion of the diffuse nucleoid camouflages an underlying active mechanism. Several genes involved in Chromosome Segregation in bacteria have now been defined; their possible functions are discussed.