scholarly journals Defining the consequences of endogenous genetic variation within a novel family of Schizosaccharomyces pombe heterochromatin nucleating sequences

2021 ◽  
Author(s):  
Arati Joshi ◽  
Meryl J Musicante ◽  
Bayly S Wheeler
Keyword(s):  
Genetic Variation ◽  
Schizosaccharomyces Pombe ◽  
Chromosome Segregation ◽  
Rapid Evolution ◽  
Rnai Pathway ◽  
Centromere Function ◽  
Sister Chromatids ◽  
Conserved Domain ◽  
Centromere Assembly ◽  
The Relationship

Abstract Centromeres are essential for genetic inheritance—they prevent aneuploidy by providing a physical link between DNA and chromosome segregation machinery. In many organisms, centromeres form at sites of repetitive DNAs that help establish the chromatin architecture required for centromere function. These repeats are often rapidly evolving and subject to homogenization, which causes the expansion of novel repeats and sequence turnover. Thus, centromere sequence varies between individuals and across species. This variation can affect centromere function. We utilized Schizosaccharomyces pombe to assess the relationship between centromere sequence and structure and determine how sensitive this relationship is to genetic variation. In S. pombe, nucleating sequences within centromere repeats recruit heterochromatin via pathways that include the RNA-interference (RNAi) pathway. Heterochromatin, in turn, contributes to centromere function through its participation in three essential processes; establishment of a kinetochore, cohesion of sister chromatids, and suppression of recombination. Here, we show that a centromere element containing RevCen, a target of the RNAi pathway, establishes heterochromatin and gene silencing when relocated to a chromosome arm. Within this RevCen-containing element (RCE), a highly conserved domain is necessary for full heterochromatin nucleation but cannot establish heterochromatin independently. We characterize the ten unique RCEs in the S. pombe centromere assembly, which range from 60-100% identical, and show that all are sufficient to establish heterochromatin. These data affirm the importance of centromere repeats in establishing heterochromatin and suggest there is flexibility within the sequences that mediate this process. Such flexibility may preserve centromere function despite the rapid evolution of centromere repeats.

Co-ordination of cytokinesis with chromosome segregation

2008 ◽  
Vol 36 (3) ◽  
pp. 387-390 ◽  
Author(s):  
Manuel Mendoza ◽  
Yves Barral
Keyword(s):  
Schizosaccharomyces Pombe ◽  
Chromosome Segregation ◽  
Cleavage Plane ◽  
Budding Yeast ◽  
Sister Chromatids ◽  
Higher Eukaryotes ◽  
Spindle Elongation

During anaphase, the spindle pulls the sister kinetochores apart until the sister chromatids are fully separated from each other. Subsequently, cytokinesis cleaves between the two separated chromosome masses to form two nucleated cells. Results from Schizosaccharomyces pombe suggested that cytokinesis and chromosome segregation are not co-ordinated with each other. However, recent studies indicate that, at least in budding yeast, a checkpoint called NoCut prevents abscission when spindle elongation is impaired, and might delay cytokinesis until all chromosomes are pulled out of the cleavage plane. Here, we discuss this possibility and summarize evidence suggesting that such a checkpoint is likely to be conserved in higher eukaryotes.

scholarly journals Keeping the Centromere under Control: A Promising Role for DNA Methylation

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 912 ◽  
Author(s):  
Scelfo ◽  
Fachinetti
Keyword(s):  
Dna Methylation ◽  
Chromosome Segregation ◽  
Dna Sequences ◽  
Genetic Material ◽  
Methylation Pattern ◽  
Repetitive Dna Sequences ◽  
Centromeric Dna ◽  
Centromere Function ◽  
Aberrant Dna Methylation ◽  
The Relationship

In order to maintain cell and organism homeostasis, the genetic material has to be faithfully and equally inherited through cell divisions while preserving its integrity. Centromeres play an essential task in this process; they are special sites on chromosomes where kinetochores form on repetitive DNA sequences to enable accurate chromosome segregation. Recent evidence suggests that centromeric DNA sequences, and epigenetic regulation of centromeres, have important roles in centromere physiology. In particular, DNA methylation is abundant at the centromere, and aberrant DNA methylation, observed in certain tumors, has been correlated to aneuploidy and genomic instability. In this review, we evaluate past and current insights on the relationship between centromere function and the DNA methylation pattern of its underlying sequences.

scholarly journals Ago1 and Dcr1, Two Core Components of the RNA Interference Pathway, Functionally Diverge from Rdp1 in Regulating Cell Cycle Events in Schizosaccharomyces pombe

2004 ◽  
Vol 15 (3) ◽  
pp. 1425-1435 ◽  
Author(s):  
Jon B. Carmichael ◽  
Patrick Provost ◽  
Karl Ekwall ◽  
Tom C. Hobman
Keyword(s):  
Cell Cycle ◽  
Rna Interference ◽  
Schizosaccharomyces Pombe ◽  
Fission Yeast ◽  
Chromosome Segregation ◽  
Control Cell ◽  
Cell Cycle Checkpoints ◽  
Rnai Pathway ◽  
Small Interfering Rnas ◽  
Heterochromatin Formation

In the fission yeast Schizosaccharomyces pombe, three genes that function in the RNA interference (RNAi) pathway, ago1+, dcr1+, and rdp1+, have recently been shown to be important for timely formation of heterochromatin and accurate chromosome segregation. In the present study, we present evidence that null mutants for ago1+ and dcr1+ but not rdp1+, exhibit abnormal cytokinesis, cell cycle arrest deficiencies, and mating defects. Subsequent analyses showed that ago1+ and dcr1+ are required for regulated hyperphosphorylation of Cdc2 when encountering genotoxic insults. Because rdp1+ is dispensable for this process, the functions of ago1+ and dcr1+ in this pathway are presumably independent of their roles in RNAi-mediated heterochromatin formation and chromosome segregation. This was further supported by the finding that ago1+ is a multicopy suppressor of the S-M checkpoint deficiency and cytokinesis defects associated with loss of Dcr1 function, but not for the chromosome segregation defects of this mutant. Accordingly, we conclude that Dcr1-dependent production of small interfering RNAs is not required for enactment and/or maintenance of certain cell cycle checkpoints and that Ago1 and Dcr1 functionally diverge from Rdp1 to control cell cycle events in fission yeast. Finally, exogenous expression of hGERp95/EIF2C2/hAgo2, a human Ago1 homolog implicated in posttranscriptional gene silencing, compensated for the loss of ago1+ function in S. pombe. This suggests that PPD proteins may also be important for regulation of cell cycle events in higher eukaryotes.

scholarly journals The centromere enhancer mediates centromere activation in Schizosaccharomyces pombe.

1997 ◽  
Vol 17 (6) ◽  
pp. 3305-3314 ◽  
Author(s):  
V K Ngan ◽  
L Clarke
Keyword(s):  
Schizosaccharomyces Pombe ◽  
Chromosome Segregation ◽  
Dna Sequences ◽  
Direct Evidence ◽  
Central Core ◽  
Specific Sequence ◽  
Circular Dna ◽  
Centromere Function

The centromere enhancer is a functionally important DNA region within the Schizosaccharomyces pombe centromeric K-type repeat. We have previously shown that addition of the enhancer and cen2 centromeric central core to a circular minichromosome is sufficient to impart appreciable centromere function. A more detailed analysis of the enhancer shows that it is dispensable for centromere function in a cen1-derived minichromosome containing the central core and the remainder of the K-type repeat, indicating that the critical centromeric K-type repeat, like the central core, is characterized by functional redundancy. The centromeric enhancer is required, however, for a central core-carrying minichromosome to exhibit immediate centromere activity when the circular DNA is introduced via transformation into S. pombe. This immediate activation is probably a consequence of a centromere-targeted epigenetic system that governs the chromatin architecture of the region. Moreover, our studies show that two entirely different DNA sequences, consisting of elements derived from two native centromeres, can display centromere function. An S. pombe CENP-B-like protein, Abp1p/Cbp1p, which is required for proper chromosome segregation in vivo, binds in vitro to sites within and adjacent to the modular centromere enhancer, as well as within the centromeric central cores. These results provide direct evidence in fission yeast of a model, similar to one proposed for mammalian systems, whereby no specific sequence is necessary for centromere function but certain classes of sequences are competent to build the appropriate chromatin foundation upon which the centromere/kinetochore can be formed and activated.

scholarly journals Evolution and evolvability: celebrating Darwin 200

2008 ◽  
Vol 5 (1) ◽  
pp. 44-46 ◽  
Author(s):  
John F.Y Brookfield
Keyword(s):  
Genetic Variation ◽  
Natural Selection ◽  
Time Scales ◽  
Evolutionary Change ◽  
Adaptive Mutation ◽  
Genetic Covariances ◽  
The Relationship ◽  
The Way

The concept of ‘evolvability’ is increasingly coming to dominate considerations of evolutionary change. There are, however, a number of different interpretations that have been put on the idea of evolvability, differing in the time scales over which the concept is applied. For some, evolvability characterizes the potential for future adaptive mutation and evolution. Others use evolvability to capture the nature of genetic variation as it exists in populations, particularly in terms of the genetic covariances between traits. In the latter use of the term, the applicability of the idea of evolvability as a measure of population's capacity to respond to natural selection rests on one, but not the only, view of the way in which we should envisage the process of natural selection. Perhaps the most potentially confusing aspects of the concept of evolvability are seen in the relationship between evolvability and robustness.

scholarly journals Genes Involved in Sister Chromatid Separation and Segregation in the Budding Yeast Saccharomyces cerevisiae

Genetics ◽  
2001 ◽  
Vol 159 (2) ◽  
pp. 453-470
Author(s):  
Sue Biggins ◽  
Needhi Bhalla ◽  
Amy Chang ◽  
Dana L Smith ◽  
Andrew W Murray
Keyword(s):  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Mitotic Spindle ◽  
Budding Yeast ◽  
Temperature Sensitive ◽  
Chromosome Behavior ◽  
Yeast Saccharomyces Cerevisiae ◽  
Sister Chromatids ◽  
Marked Chromosome ◽  
Sister Chromatid Separation

Abstract Accurate chromosome segregation requires the precise coordination of events during the cell cycle. Replicated sister chromatids are held together while they are properly attached to and aligned by the mitotic spindle at metaphase. At anaphase, the links between sisters must be promptly dissolved to allow the mitotic spindle to rapidly separate them to opposite poles. To isolate genes involved in chromosome behavior during mitosis, we microscopically screened a temperature-sensitive collection of budding yeast mutants that contain a GFP-marked chromosome. Nine LOC (loss of cohesion) complementation groups that do not segregate sister chromatids at anaphase were identified. We cloned the corresponding genes and performed secondary tests to determine their function in chromosome behavior. We determined that three LOC genes, PDS1, ESP1, and YCS4, are required for sister chromatid separation and three other LOC genes, CSE4, IPL1, and SMT3, are required for chromosome segregation. We isolated alleles of two genes involved in splicing, PRP16 and PRP19, which impair α-tubulin synthesis thus preventing spindle assembly, as well as an allele of CDC7 that is defective in DNA replication. We also report an initial characterization of phenotypes associated with the SMT3/SUMO gene and the isolation of WSS1, a high-copy smt3 suppressor.

scholarly journals Pericentric chromatin loops function as a nonlinear spring in mitotic force balance

2013 ◽  
Vol 200 (6) ◽  
pp. 757-772 ◽  
Author(s):  
Andrew D. Stephens ◽  
Rachel A. Haggerty ◽  
Paula A. Vasquez ◽  
Leandra Vicci ◽  
Chloe E. Snider ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Spindle Assembly Checkpoint ◽  
Force Balance ◽  
Nonlinear Spring ◽  
Sister Chromatids ◽  
Spindle Dynamics ◽  
Restoring Forces ◽  
Cross Links ◽  
Mean And Variance

The mechanisms by which sister chromatids maintain biorientation on the metaphase spindle are critical to the fidelity of chromosome segregation. Active force interplay exists between predominantly extensional microtubule-based spindle forces and restoring forces from chromatin. These forces regulate tension at the kinetochore that silences the spindle assembly checkpoint to ensure faithful chromosome segregation. Depletion of pericentric cohesin or condensin has been shown to increase the mean and variance of spindle length, which have been attributed to a softening of the linear chromatin spring. Models of the spindle apparatus with linear chromatin springs that match spindle dynamics fail to predict the behavior of pericentromeric chromatin in wild-type and mutant spindles. We demonstrate that a nonlinear spring with a threshold extension to switch between spring states predicts asymmetric chromatin stretching observed in vivo. The addition of cross-links between adjacent springs recapitulates coordination between pericentromeres of neighboring chromosomes.

Genetic variation and relationship of ultrasonic measures and carcass composition in Suffolk cross lambs

1996 ◽  
Vol 1996 ◽  
pp. 111-111
Author(s):  
V.C. Flamarique ◽  
R.M. Lewis ◽  
G. Simm
Keyword(s):  
Genetic Variation ◽  
Selection Criteria ◽  
Live Weight ◽  
Ultrasonic Measurement ◽  
Carcass Composition ◽  
Selection Indices ◽  
Terminal Sire ◽  
Relationship Of ◽  
The Relationship

Excess fat in lamb is regarded as an important reason for less lamb meat being purchased by consumers. This has encouraged the development and use (particularly in Terminal Sire breeds) of selection indices that can identify animals that will sire leaner progeny. These indices usually include live weight and in vivo predictors of body composition, such as an ultrasonic measurement of muscle and fat depth, as selection criteria (Simm and Dingwall, 1989). But the usefulness of such in vivo measurements as predictors of carcass composition depends on the correlation between, and the variation in, live and carcass measures. The objectives of this study were to determine the strength of the relationship between ultrasound and dissection measures of carcass composition, and the degree of genetic variation in these measures, in crossbred progeny of Suffolk rams.

Identification of DNA regions required for mitotic and meiotic functions within the centromere of Schizosaccharomyces pombe chromosome I

1991 ◽  
Vol 11 (4) ◽  
pp. 2206-2215
Author(s):  
K M Hahnenberger ◽  
J Carbon ◽  
L Clarke
Keyword(s):  
Schizosaccharomyces Pombe ◽  
Sister Chromatid ◽  
Inverted Repeat ◽  
Distal Portion ◽  
Central Core ◽  
Inverted Repeat Region ◽  
Artificial Chromosomes ◽  
Centromere Function ◽  
Chromosome I ◽  
Meiosis I

We have determined the structural organization and functional roles of centromere-specific DNA sequence repeats in cen1, the centromere region from chromosome I of the fission yeast Schizosaccharomyces pombe. cen1 is composed of various classes of repeated sequences designated K', K"(dgl), L, and B', arranged in a 34-kb inverted repeat surrounding a 4- to 5-kb nonhomologous central core. Artificial chromosomes containing various portions of the cen1 region were constructed and assayed for mitotic and meiotic centromere function in S. pombe. Deleting K' and L from the distal portion of one arm of the inverted repeat had no effect on mitotic centromere function but resulted in greatly increased precocious sister chromatid separation in the first meiotic division. A centromere completely lacking K' and L, but containing the central core, one copy of B' and K" in one arm, and approximately 2.5 kb of the core-proximal portion of B' in the other arm, was also fully functional mitotically but again did not maintain sister chromatid attachment in meiosis I. However, deletion of K" from this minichromosome resulted in complete loss of centromere function. Thus, one copy of at least a portion of the K" (dgl) repeat is absolutely required but is not sufficient for S. pombe centromere function. The long centromeric inverted-repeat region must be relatively intact to maintain sister chromatid attachment in meiosis I.

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