Yeast Apoptosis Research Articles

Yeast Programmed Cell Death: An Intricate Puzzle

Yeasts as eukaryotic microorganisms with simple, well known and tractable genetics, have long been powerful model systems for studying complex biological phenomena such as the cell cycle or vesicle fusion. Until recently, yeast has been assumed as a cellular 'clean room' to study the interactions and the mechanisms of action of mammalian apoptotic regulators. However, the finding of an endogenous programmed cell death (PCD) process in yeast with an apoptotic phenotype has turned yeast into an 'unclean' but even more powerful model for apoptosis research. Yeast cells appear to possess an endogenous apoptotic machinery including its own regulators and pathway(s). Such machinery may not exactly recapitulate that of mammalian systems but it represents a simple and valuable model which will assist in the future understanding of the complex connections between apoptotic and non-apoptotic mammalian PCD pathways. Following this line of thought and in order to validate and make the most of this promising cell death model, researchers must undoubtedly address the following issues: what are the crucial yeast PCD regulators? How do they play together? What are the cell death pathways shared by yeast and mammalian PCD? Solving these questions is currently the most pressing challenge for yeast cell death researchers.

Role of mitochondria in the pheromone- and amiodarone-induced programmed death of yeast

Although programmed cell death (PCD) is extensively studied in multicellular organisms, in recent years it has been shown that a unicellular organism, yeast Saccharomyces cerevisiae, also possesses death program(s). In particular, we have found that a high doses of yeast pheromone is a natural stimulus inducing PCD. Here, we show that the death cascades triggered by pheromone and by a drug amiodarone are very similar. We focused on the role of mitochondria during the pheromone/amiodarone-induced PCD. For the first time, a functional chain of the mitochondria-related events required for a particular case of yeast PCD has been revealed: an enhancement of mitochondrial respiration and of its energy coupling, a strong increase of mitochondrial membrane potential, both events triggered by the rise of cytoplasmic [Ca2+], a burst in generation of reactive oxygen species in center o of the respiratory chain complex III, mitochondrial thread-grain transition, and cytochrome c release from mitochondria. A novel mitochondrial protein required for thread-grain transition is identified.

Yeast apoptosis debate continues

Yeast, as a unicellular organism, would seem to benefit most from self-preservation. But yeast altruism, in the form of apoptosis, is a new-found, if controversial, field of study. Many doubt the validity of experiments supporting programmed cell death in yeast and call for better controls. In this issue, the debate continues with two new articles that suggest that yeast cells do organize their own deaths—for the sake of their brethren. Figure AIF leaves mitochondria for the nucleus in aged yeast cells (bottom). Biologists often address how a phenomenon occurs, but seldom why. For the yeast apoptosis field, however, why is a painfully obvious question. On page 1055, Fabrizio et al. suggest a method to the madness. They show that yeast populations survive better in the long run when they initiate an early death program through superoxide. Superoxides are produced by the everyday activities of life, but their mutational and death-inducing activities can be curtailed by superoxide dismutases (Sods). The authors find that Sods are normally down-regulated in older yeast cultures, which are surviving in nutrient-poor medium, leading to cell death. Mutants that circumvented this programmed death mechanism by maintaining high Sod activity had extended life spans. These long-lived populations, however, were unable to repopulate their culture once most of the cells died, a phenomenon known as adaptive regrowth. As a result, in competition experiments, strains that initiated early death eventually outgrew the wild type. Early death probably allows the best-adapted cells in a population to reproduce before they are too old by using nutrients left behind by the dead yeasts. Superoxides are mutation inducers. The higher mutation rates that the authors noted in wild-type and other short-lived populations might impart surviving cells with the ability to use newly available nutrients rather than rely on the vanishing original supply. Mathematical models of adaptive regrowth based on experimental measurements of growth and mutation rates confirmed that long-lived populations are less able to survive under changing growth conditions. The group has shown before that aging is similar among yeast and higher eukaryotes. The finding that yeast programs its own aging for altruistic reasons raises the pessimistic possibility that our own life span is best left similarly limited. The authors do not insist that superoxide-mediated death must be apoptotic, but hallmarks of mammalian apoptosis were seen, including chromatin condensation, cytosolic acidification, and extracellular exposure of phosphatidyl serine. Another parallel with mammalian apoptosis, AIF-induced cell death, is revealed in an article by Wissing et al. (page 969). AIF is a mitochondrial protein that moves to the nucleus in response to apoptosis-inducing stimuli and then triggers DNA degradation. Wissing et al. show that similar translocation and degradation events occur in yeast apoptosis and that its loss delays age- or peroxide-induced death, accompanied by chromatin condensation and DNA fragmentation. Overexpression of yeast AIF sensitized cells to death in response to low levels of peroxide in a pathway that was partly dependent on the yeast caspase-like protein YCA1. Many still remain skeptical, however, about the idea of yeast apoptosis. A recent report by Wysocki and Kron (J. Cell Biol. 166:311–316) suggested that some past evidence of apoptosis was artifactual and that death is independent of YCA1. Proponents of yeast apoptosis counter that Wysocki and Kron used extreme death-inducing conditions, which could lead to nonapoptotic or caspase-independent death. They say that the identification of so many yeast counterparts of mammalian apoptotic proteins, including YCA1, Cdc48, Cdc6, and the caspase regulator OMI, suggests that the pathway is ancient and conserved. Things may be more complicated for some of the mammalian proteins implicated in apoptosis. Past evidence, for instance, suggests that the loss of AIF in mammalian cells makes the cells more, not less, susceptible to death. If yeast do undergo apoptosis, scientists will be better able to do experiments that would be difficult in mammalian cells. Wissing et al. hope to find suppressors of AIF overexpression, for example. For now, it seems, they are still fighting to prove that apoptosis is a real phenomenon in yeast. We therefore await the next battle in this deadly war. ▪

An AIF orthologue regulates apoptosis in yeast.

Apoptosis-inducing factor (AIF), a key regulator of cell death, is essential for normal mammalian development and participates in pathological apoptosis. The proapoptotic nature of AIF and its mode of action are controversial. Here, we show that the yeast AIF homologue Ynr074cp controls yeast apoptosis. Similar to mammalian AIF, Ynr074cp is located in mitochondria and translocates to the nucleus of yeast cells in response to apoptotic stimuli. Purified Ynr074cp degrades yeast nuclei and plasmid DNA. YNR074C disruption rescues yeast cells from oxygen stress and delays age-induced apoptosis. Conversely, overexpression of Ynr074cp strongly stimulates apoptotic cell death induced by hydrogen peroxide and this effect is attenuated by disruption of cyclophilin A or the yeast caspase YCA1. We conclude that Ynr074cp is a cell death effector in yeast and rename it AIF-1 (Aif1p, gene AIF1).

The Second International Meeting on Yeast Apoptosis (IMYA 2), Smolenice, Slovak Republic, 17-20 September 2003.

We know it is only dying yeast but we all like it more and more… Two years ago a group of researchers sharing the same scientific interest decided that an IMYA meeting should be organized every year. That initiative aimed at regularly joining researchers working on the very new and growing field of programmed cell death (PCD) and aging in yeast. The first IMYA meeting was held in 2002 in Braga, Portugal. The 2003 annual meeting was held in Smolenice, Slovak Republic, and it was organised by Jordan Kolarov (Comenius University, Bratislava), Ludmila Sabova (Slovak Academy of Sciences), Zdena Palkova (Charles University, Prague), Alena Pichova (Czech Academy of Sciences, Prague) and Martin Kucej (Comenius University, Bratislava). The beautiful castle of Smolenice and its wonderful surrounding landscape offered 60 participants (from 10 European countries, USA, Australia, India, Iran, South Korea and Japan) a unique stay during the three-days meeting. They could share and discuss, in a very quiet and relaxed atmosphere, their latest scientific results and enjoy a visit to natural caves and a castle in the vicinity, as well as the taste of Slovak wines and food and the sound of folk music and songs. The scientific programme started with an opening lecture on Cellular responses to reactive oxygen species by Ian Dawes (University of New South Wales, Sydney, Australia) and included 23 oral presentations and fifteen posters, mostly covered by the five topic sessions on: (1) Evolutionary aspects of apoptosis; (2) The yeast cell death pathway; (3) Aging and apoptosis relationship; (4) Bcl-2 proteins and mitochondria; and (5) Exogenously triggered yeast cell death. Ian Dawes presented a picture of …

The S. cerevisiae HtrA-like protein Nma111p is a nuclear serine protease that mediates yeast apoptosis.

The yeast S. cerevisiae can undergo programmed cell death that exhibits the typical cellular markers of apoptosis. The mammalian HtrA2 protein was recently reported to mediate apoptosis in a serine-protease-dependent manner owing to its ability to antagonise the inhibitor of apoptosis protein XIAP. Here, we report the identification and characterisation of the S. cerevisiae HtrA-like protein, which we termed Nma111p (for nuclear mediator of apoptosis), as a mediator of yeast apoptosis. Nma111p is a nuclear protein that, under cellular stress conditions (i.e. at elevated temperature or after induction of apoptosis by H2O2), tends to aggregate inside the nucleus without its expression level being upregulated, suggesting that aggregation of Nma111p is correlated to its death-mediating character. Nma111p belongs to the HtrA family of serine proteases and its pro-apoptotic activity depends on its serine-protease activity. Yeast cells that lack Nma111p survive better at 50 degrees C than wild-type cells and the cells show no apoptotic hallmarks, such as chromatin condensation and fragmentation, or accumulation of reactive oxygen species, after the induction of apoptosis by H2O2. By contrast, overexpression of Nma111p enhances apoptotic-like cell death. Therefore, Nma111p, like its mammalian homologue HtrA2, mediates apoptosis.

2nd International Meeting on Yeast Apoptosis

2nd International Meeting on Yeast Apoptosis

2nd International Meeting on Yeast Apoptosis

2nd International Meeting on Yeast Apoptosis

Pseudomonas type III effector AvrPtoB induces plant disease susceptibility by inhibition of host programmed cell death.

The AvrPtoB type III effector protein is conserved among diverse genera of plant pathogens suggesting it plays an important role in pathogenesis. Here we report that Pseudomonas AvrPtoB acts inside the plant cell to inhibit programmed cell death (PCD) initiated by the Pto and Cf9 disease resistance proteins and, remarkably, the pro-apoptotic mouse protein Bax. AvrPtoB also suppressed PCD in yeast, demonstrating that AvrPtoB functions as a cell death inhibitor across kingdoms. Using truncated AvrPtoB proteins, we identified distinct N- and C-terminal domains of AvrPtoB that are sufficient for host recognition and PCD inhibition, respectively. We also identified a novel resistance phenotype, Rsb, that is triggered by an AvrPtoB truncation disrupted in the anti-PCD domain. A Pseudomonas syringae pv. tomato DC3000 strain with a chromosomal mutation in the AvrPtoB C-terminus elicited Rsb-mediated immunity in previously susceptible tomato plants and disease was restored when full-length AvrPtoB was expressed in trans. Thus, our results indicate that a type III effector can induce plant susceptibility to bacterial infection by inhibiting host PCD.

A truncated form of KlLsm4p and the absence of factors involved in mRNA decapping trigger apoptosis in yeast.

The LSM4 gene of Saccharomyces cerevisiae codes for an essential protein involved in pre-mRNA splicing and also in mRNA decapping, a crucial step for mRNA degradation. We previously demonstrated that the first 72 amino acids of the Kluyveromyces lactis Lsm4p (KlLsm4p), which contain the Sm-like domains, can restore cell viability in both K. lactis and S. cerevisiae cells not expressing the endogenous protein. However, the absence of the carboxy-terminal region resulted in a remarkable loss of viability in stationary phase cells (). Herein, we demonstrate that S. cerevisiae cells expressing the truncated LSM4 protein of K. lactis showed the phenotypic markers of yeast apoptosis such as chromatin condensation, DNA fragmentation, and accumulation of reactive oxygen species. The study of deletion mutants revealed that apoptotic markers were clearly evident also in strains lacking genes involved in mRNA decapping, such as LSM1, DCP1, and DCP2, whereas a slight effect was observed in strains lacking the genes DHH1 and PAT1. This is the first time that a connection between mRNA stability and apoptosis is reported in yeast, pointing to mRNA decapping as the crucial step responsible of the observed apoptotic phenotypes.

Death Comes for the Fungus: Yeast protein mimics mammalian cell suicide trigger (Apoptosis)

For decades, yeast have taught scientists how cells live; now it seems that the microbes might also reveal how cells die. A yeast protein behaves similarly to mammalian proteins that coordinate a cell suicide mechanism, according to new work. If the protein's function is confirmed, it will help build the argument that yeast and mammalian cells can die by similar means. The study hints that yeast could reveal the evolutionary origins of this death wish. Animals use a lethal tool called apoptosis to dispose of cells that have outlived their usefulness or that pose a threat to the organism. Protein-cutting enzymes called caspases regulate the process: When cells encounter damaging agents such as hydrogen peroxide, caspases come to life and activate molecules that set apoptosis in motion. Although some results have hinted that yeast can die by a process similar to apoptosis, the fact that scientists hadn't found a functional yeast caspase left many researchers skeptical. Two years ago, researchers discovered that the genomes of many organisms, including plants and yeast, harbor genes called metacaspases that distantly resemble mammalian caspase genes, but no one knew their function. Madeo and colleagues investigated how the yeast metacaspase gene, which they named YCA1 , affected yeast vitality. They engineered yeast to produce large amounts of YCA1 protein. Then they treated cultures with hydrogen peroxide and measured the fraction of cells that could grow on a petri dish. An abnormally high percentage of modified cells could not. The dead cells showed signs of having undergone apoptosis; for instance, they contained chopped-up DNA. But cells with abundant YCA1 survived if they also lacked a protein whose mammalian counterpart lies downstream of caspases in the apoptosis pathway. In addition, whereas extra YCA1 rendered cells susceptible to hydrogen peroxide, absence of the protein hardened them against the chemical insult. The results suggest that YCA1 triggers cell death in yeast. Additional experiments revealed that the YCA1 protein performs caspaselike biochemical feats. For example, the researchers tested the ability of yeast extracts to cleave three of the proteins that mammalian caspases target. They treated cells with hydrogen peroxide, ground them up, and found that material from yeast that pumped out YCA1 cut the test molecules much faster than that from control strains. The authors conclude that YCA1 regulates yeast apoptosis by a protein-cutting activity reminiscent of that exhibited by mammalian caspases. Because the yeast gene's sequence isn't very close to that of mammalian caspases, scientists hadn't predicted such behavior. "I'm really quite surprised," says biochemist Guy Salvesen of the Burnham Institute in La Jolla, California. But to be convinced that YCA1 is a bona fide caspase, he would like to see evidence that the protein snips caspase substrates specifically and not other molecules. Other researchers still wonder whether yeast are really undergoing apoptosis. "It could be an ancient form of cell death that you probably ought to call something else," says biochemist Lisa Ellerby of the Buck Institute for Age Research in Novato, California. Even if that's true, she says, understanding cell death in yeast could reveal how apoptosis evolved. --R. John Davenport; suggested by Greg Liszt F. Madeo, E. Herker, C. Maldener, S. Wissing, S. Lächelt, M. Herlan, M. Fehr, K. Lauber, S. J. Sigrist, S. Wesselborg, K.-U. Fröhlich, A caspase-related protease regulates apoptosis in yeast. Mol. Cell 9 , 911-917 (2002). [Abstract] [Full Text]

A Caspase-Related Protease Regulates Apoptosis in Yeast

Yeast can undergo cell death accompanied by cellular markers of apoptosis. However, orthologs of classical mammalian apoptosis regulators appeared to be missing from the yeast genome, challenging a common mechanism of yeast and mammalian apoptosis. Here we investigate Yor197w, a yeast protein with structural homology to mammalian caspases, and demonstrate caspase-like processing of the protein. Hydrogen peroxide treatment induces apoptosis together with a caspase-like enzymatic activity in yeast. This response is completely abrogated after disruption and strongly stimulated after overexpression of Yor197w. Yor197w also mediates the death process within chronologically aged cultures, pointing to a physiological role in elimination of overaged cells. We conclude that Yor197w indeed functions as a bona fide caspase in yeast and propose the name Yeast Caspase-1 (YCA1, gene YCA1).

Salt causes ion disequilibrium-induced programmed cell death in yeast and plants.

Programmed cell death (PCD) is a fundamental cellular process conserved in metazoans, plants and yeast. Evidence is presented that salt induces PCD in yeast and plants because of an ionic, rather than osmotic, etiology. In yeast, NaCl inhibited growth and caused a time-dependent reduction in viability that was preceded by DNA fragmentation. NaCl also induced the cytological hallmarks of lysigenous-type PCD, including nuclear fragmentation, vacuolation and lysis. The human anti-apoptotic protein Bcl-2 increased salt tolerance of wild-type yeast strain and calcineurin-deficient yeast mutant (cnb1Delta) that is defective for ion homeostasis, but had no effect on the NaCl or sorbitol sensitivity of the osmotic hypersensitive hog1Delta mutant -- results that further link PCD in the response to the ion disequilibrium under salt stress. Bcl-2 suppression of cnb1Delta salt sensitivity was ENA1 (P-type ATPase gene)-dependent, due in part to transcriptional activation. Salt-induced PCD (TUNEL staining and DNA laddering) in primary roots of both Arabidopsis thaliana wild type (Col-1 gl1) and sos1 (salt overly sensitive) mutant seedlings correlated positively with treatment lethality. Wild-type plants survived salt stress levels that were lethal to sos1 plants because secondary roots were produced from the shoot/root transition zone. PCD-mediated elimination of the primary root in response to salt shock appears to be an adaptive mechanism that facilitates the production of roots more able to cope with a saline environment. Both salt-sensitive mutants of yeast (cnb1Delta) and Arabidopsis (sos1) exhibit substantially more profound PCD symptoms, indicating that salt-induced PCD is mediated by ion disequilibrium.

Vesicle-associated Membrane Protein ofArabidopsis Suppresses Bax-induced Apoptosis in Yeast Downstream of Oxidative Burst

Programmed cell death (PCD) in many systems is controlled by relative amounts of the apoptosis-regulating proteins Bax and Bcl-2 through homo- or heterodimerization. Here we show that Bax-induced PCD of yeast was suppressed by transformation with a vesicle-associated membrane protein from Arabidopsis (AtVAMP), which was isolated by screening a cDNA expression library against sugar-induced cell death in yeast. AtVAMP expression blocked Bax-induced PCD downstream of oxidative burst. AtVAMP also prevented H(2)O(2)-induced apoptosis in yeast and in Arabidopsis cells. Reduced oxidation of lipids and plasma membrane proteins was detected in the AtVAMP-transformed yeast, suggesting improved membrane repair. Inhibition of intracellular vesicle trafficking by brefeldin A induced apoptosis from a sublethal concentration of H(2)O(2). No protection occurred by overexpression of the yeast homolog SCN2. However, efficient suppression of yeast PCD occurred by expression of a chimeric gene, composed of the conserved domains from yeast, fused to the variable N-terminal domain from Arabidopsis, resulting in exchange of the proline-rich N-terminal domain of SCN2 with a proline-poor Arabidopsis sequence. Our results suggest that intracellular vesicle traffic can regulate execution of apoptosis by affecting the rate of membrane recycling and that the proline-rich N-terminal domain of VAMP inhibited this process.

Aged mother cells of Saccharomyces cerevisiae show markers of oxidative stress and apoptosis

Recently, we and others have shown that genetic and environmental changes that increase the load of yeast cells with reactive oxygen species (ROS) lead to a shortening of the life span of yeast mother cells. Deletions of yeast genes coding for the superoxide dismutases or the catalases, as well as changes in atmospheric oxygen concentration, considerably shortened the life span. The presence of the physiological antioxidant glutathione, on the other hand, increased the life span of yeast cells. Taken together, these results pointed to a role for oxygen in the yeast ageing process. Here, we show by staining with dihydrorhodamine that old yeast mother cells isolated by elutriation, but not young cells, contain ROS that are localized in the mitochondria. A relatively large proportion of the old mother cells shows phenotypic markers of yeast apoptosis, i.e. TUNEL (TdT-mediated dUTP nick end labelling) and annexin V staining. Although it has been shown previously that apoptosis in yeast can be induced by a cdc48 allele, by expressing pro-apoptotic human cDNAs or by stressing the cells with hydrogen peroxide, we are now showing a physiological role for apoptosis in unstressed but aged wild-type yeast mother cells.

Apoptosis in yeast – a monocellular organism exhibits altruistic behaviour

Apoptosis is a highly regulated form of programmed cell death crucial for life and health in metazoan animals. Apoptosis is defined by a set of cytological alterations. The recent discovery of these markers in yeast indicates the presence of the basic mechanisms of apoptosis already in unicellular eukaryotes. Oxygen radicals regulate both mammalian and yeast apoptosis. We suggest that apoptosis originated in unicellular organisms as an altruistic response to severe oxidative damage. Later, cells developed mechanisms to purposely produce reactive oxygen species as a regulator of apoptosis. Yeast may become an important model to investigate the conserved steps of apoptosis.

Substantial background reduction in ligase-based apoptosis detection using newly designed hairpin oligonucleotide probes.

BioTechniquesVol. 27, No. 6 BenchmarksOpen AccessSubstantial Background Reduction in Ligase-Based Apoptosis Detection Using Newly Designed Hairpin Oligonucleotide ProbesVladimir V. Didenko, Denise J. Boudreaux & David S. BaskinVladimir V. Didenko*Address correspondence to Dr. Vladimir V. Didenko, Department of Neurosurgery, Baylor College of Medicine, 6560 Fannin, Suite 944, Houston, TX 77030, USA. Internet: E-mail Address: vdidenko@bcm.tmc.eduBaylor College of Medicine, Houston, TX, USASearch for more papers by this author, Denise J. BoudreauxBaylor College of Medicine, Houston, TX, USASearch for more papers by this author & David S. BaskinBaylor College of Medicine, Houston, TX, USASearch for more papers by this authorPublished Online:22 Aug 2018https://doi.org/10.2144/99276bm09AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinkedInRedditEmail FiguresReferencesRelatedDetailsCited ByAtorvastatin Therapy during the Peri-Infarct Period Attenuates Left Ventricular Dysfunction and Remodeling after Myocardial Infarction28 September 2011 | PLoS ONE, Vol. 6, No. 9In Situ Ligation: A Decade and a Half of Experience15 October 2010In Situ Ligation Simplified: Using PCR Fragments for Detection of Double-Strand DNA Breaks in Tissue Sections15 October 2010Quantification and calibration of images in fluorescence microscopyAnalytical Biochemistry, Vol. 404, No. 2PREVENTION OF HEMORRHAGIC SHOCK-INDUCED INTESTINAL TISSUE INJURY BY GLUTAMINE VIA HEME OXYGENASE-1 INDUCTIONShock, Vol. 31, No. 1PROTECTIVE ROLE OF HEME OXYGENASE 1 IN THE INTESTINAL TISSUE INJURY IN HEMORRHAGIC SHOCK IN RATSShock, Vol. 29, No. 2Differential regulation of Akt, caspases and MAP kinases underlies smooth muscle cell apoptosis during aortic remodelling in SHR treated with amlodipine29 January 2009 | British Journal of Pharmacology, Vol. 151, No. 8Lack of osteopontin improves cardiac function in streptozotocin-induced diabetic miceAmerican Journal of Physiology-Heart and Circulatory Physiology, Vol. 292, No. 1Characterization of DNA Damage in Yeast Apoptosis Induced by Hydrogen Peroxide, Acetic Acid, and Hyperosmotic ShockMolecular Biology of the Cell, Vol. 17, No. 10Prolonged Cold Ischemia in Rat Cardiac Allografts Promotes Ischemia–Reperfusion Injury and the Development of Graft Coronary Artery Disease in a Linear FashionThe Journal of Heart and Lung Transplantation, Vol. 24, No. 11Pro- and anti-apoptotic evidence for cholinergic denervation and hippocampal sympathetic ingrowth in rat dorsal hippocampusExperimental Neurology, Vol. 194, No. 1Phosphodiesterase-5 Inhibition With Sildenafil Attenuates Cardiomyocyte Apoptosis and Left Ventricular Dysfunction in a Chronic Model of Doxorubicin CardiotoxicityCirculation, Vol. 111, No. 13Positive Contribution of Pathogenic Mutations in the Mitochondrial Genome to the Promotion of Cancer by Prevention from Apoptosis7 March 2005 | Cancer Research, Vol. 65, No. 5Semi-artificial Fluorescent Molecular Machine for DNA Damage Detection16 November 2004 | Nano Letters, Vol. 4, No. 12Overexpression of Human Copper/Zinc Superoxide Dismutase (SOD1) Suppresses Ischemia–Reperfusion Injury and Subsequent Development of Graft Coronary Artery Disease in Murine Cardiac GraftsCirculation, Vol. 110, No. 11_suppl_1Early Necrotic DNA DegradationThe American Journal of Pathology, Vol. 162, No. 5Visualization of Irreparable Ischemic Damage in Brain by Selective Labeling of Double-Strand Blunt-Ended DNA Breaks1 December 2002 | Molecular Medicine, Vol. 8, No. 12Cardioselective overexpression of HO-1 prevents I/R-induced cardiac dysfunction and apoptosisAmerican Journal of Physiology-Heart and Circulatory Physiology, Vol. 283, No. 2Apoptosis of T lymphocytes invading glioblastomas multiforme: a possible tumor defense mechanismJournal of Neurosurgery, Vol. 96, No. 3DNA Probes Using Fluorescence Resonance Energy Transfer (FRET): Designs and ApplicationsVladimir V. Didenko5 September 2018 | BioTechniques, Vol. 31, No. 5Overexpression of Bcl-2 attenuates apoptosis and protects against myocardial I/R injury in transgenic miceAmerican Journal of Physiology-Heart and Circulatory Physiology, Vol. 280, No. 5Chapter 17 In situ detection of dying cells in normal and pathological tissuesLeft Ventricular Hypertrophy in Ascending Aortic Stenosis MiceCirculation, Vol. 101, No. 24 Vol. 27, No. 6 Follow us on social media for the latest updates Metrics Downloaded 40 times History Published online 22 August 2018 Published in print December 1999 Information© 2018 Author(s)PDF download

CAS, the Human Homologue of the Yeast Chromosome-Segregation Gene CSE1, in Proliferation, Apoptosis, and Cancer

Proliferation—that is, progression through the cell cycle—and apoptosis are opposing cellular mechanisms, one leading to multiplication and the other to elimination of cells. Although proliferation and apoptosis can function independently of each other, the two pathways are often linked in mammalian cells. For example, cell-cycle checkpoints control the initiation, progression, and completion of the cycle, giving cells a chance to correct mistakes before continuing with subsequent steps of the cycle.