Differential associations between impaired autobiographical memory recall and future thinking in people with and without schizophrenia.

OBJECTIVES: The ability to think about future events serves a range of important functions. People with schizophrenia show impairments in future thinking. However, whether these impairments are specific to positive or negative events and to what extent they are associated with impairments in verbal fluency and autobiographical memory remains poorly understood. METHODS: People with schizophrenia (n = 93) and people without psychiatric diagnoses (n = 111) were asked to generate future events and retrieve past autobiographical events and they also completed a test of verbal fluency. Participants also completed questionnaire measures of the positive and negative dimensions of schizophrenia and depression symptoms. RESULTS: People with schizophrenia generated significantly fewer positive and negative future events than controls. In a linear regression, the interaction between diagnosis and autobiographical memory retrieval explained a significant amount of variance in the number of future events that participants generated even when accounting for symptoms and verbal fluency. Past and future thinking abilities were correlated in controls but not in people with schizophrenia. CONCLUSIONS: People with schizophrenia may not rely on autobiographical content to imagine the future and may rely instead on semantic processes. Interventions that improve past and future thinking amongst people with schizophrenia are warranted. PRACTITIONER POINTS: Compared to control participants, people with schizophrenia have marked difficulty generating possible, positive and negative, future events. Unlike controls, for people with schizophrenia there is no relation between their ability to remember past events and their ability to think about the future. People with schizophrenia may have difficulty using their memories for their past to imagine and simulate possible future events.

Valence-related impairments in the retrieval of specific autobiographical memories amongst patients with schizophrenia.

OBJECTIVES: People with schizophrenia have difficulty recalling specific autobiographical events from their past. However, the nature of this difficulty (e.g., whether these problems are only for memories that are negative or positive) and the mechanisms associated with it remain poorly understood. METHODS: The present investigation asked patients with schizophrenia (n = 91) and healthy controls (n = 109) to recall memories related to several positive and negative cue words. Participants also completed self-report measures of rumination and depressive symptoms and a measure of verbal fluency to assess executive functioning. Participants' memories were coded for specificity (whether or not they referred to a specific event lasting <24 hr) and valence (positive vs. negative). RESULTS: Patients recalled fewer specific memories than controls and they showed particular difficulty recalling specific negative memories cued by negative words. For healthy controls, impoverished verbal fluency was associated with recall of fewer specific memories and particularly recall of fewer positive specific memories. These variables were unrelated to specificity amongst patients. Rumination was not associated with specificity in either group. CONCLUSIONS: These findings are discussed with reference to other mechanisms that might contribute towards reduced specificity in schizophrenia, such as the tendency to avoid negative affect, and the implications of this for interventions for schizophrenia and memory specificity problems. PRACTITIONER POINTS: The experience of schizophrenia is associated with problems recalling specific events from one's past. In particular, patients have difficulty recalling specific negative memories from their past. These memory problems are independent of executive functioning difficulties, ruminative tendencies, and also depression symptoms. Interventions for memory problems in schizophrenia must target the difficulty people have in recalling specific negative events.

A single nucleotide polymorphism uncovers a novel function for the transcription factor Ace2 during Candida albicans hyphal development.

Candida albicans is a major invasive fungal pathogen in humans. An important virulence factor is its ability to switch between the yeast and hyphal forms, and these filamentous forms are important in tissue penetration and invasion. A common feature for filamentous growth is the ability to inhibit cell separation after cytokinesis, although it is poorly understood how this process is regulated developmentally. In C. albicans, the formation of filaments during hyphal growth requires changes in septin ring dynamics. In this work, we studied the functional relationship between septins and the transcription factor Ace2, which controls the expression of enzymes that catalyze septum degradation. We found that alternative translation initiation produces two Ace2 isoforms. While full-length Ace2, Ace2L, influences septin dynamics in a transcription-independent manner in hyphal cells but not in yeast cells, the use of methionine-55 as the initiation codon gives rise to Ace2S, which functions as the nuclear transcription factor required for the expression of cell separation genes. Genetic evidence indicates that Ace2L influences the incorporation of the Sep7 septin to hyphal septin rings in order to avoid inappropriate activation of cell separation during filamentous growth. Interestingly, a natural single nucleotide polymorphism (SNP) present in the C. albicans WO-1 background and other C. albicans commensal and clinical isolates generates a stop codon in the ninth codon of Ace2L that mimics the phenotype of cells lacking Ace2L. Finally, we report that Ace2L and Ace2S interact with the NDR kinase Cbk1 and that impairing activity of this kinase results in a defect in septin dynamics similar to that of hyphal cells lacking Ace2L. Together, our findings identify Ace2L and the NDR kinase Cbk1 as new elements of the signaling system that modify septin ring dynamics in hyphae to allow cell-chain formation, a feature that appears to have evolved in specific C. albicans lineages.

Eng2 is a component of a dynamic protein complex required for endocytic uptake in fission yeast.

Eng2 is a glucanase required for spore release, although it is also expressed during vegetative growth, suggesting that it might play other cellular functions. Its homology to the Saccharomyces cerevisiae Acf2 protein, previously shown to promote actin polymerization at endocytic sites in vitro, prompted us to investigate its role in endocytosis. Interestingly, depletion of Eng2 caused profound defects in endocytic uptake, which were not due to the absence of its glucanase activity. Analysis of the dynamics of endocytic proteins by fluorescence microscopy in the eng2Δ strain unveiled a previously undescribed phenotype, in which assembly of the Arp2/3 complex appeared uncoupled from the internalization of the endocytic coat and resulted in a fission defect. Strikingly also, we found that Eng2-GFP dynamics did not match the pattern of other endocytic proteins. Eng2-GFP localized to bright cytosolic spots that moved around the cellular poles and occasionally contacted assembling endocytic patches just before recruitment of Wsp1, the Schizosaccharomyces pombe WASP. Interestingly, Csh3-YFP, a WASP-interacting protein, interacted with Eng2 by co-immunoprecipitation and was recruited to Eng2 in bright cytosolic spots. Altogether, our work defines a novel endocytic functional module, which probably couples the endocytic coat to the actin module.

PrsQ2, a small periplasmic protein involved in increased uranium resistance in the bacterium Cupriavidus metallidurans.

Uranium contamination is a widespread problem caused by natural and anthropogenic activities. Although microorganisms thrive in uranium-contaminated environments, little is known about the actual molecular mechanisms mediating uranium resistance. Here, we investigated the resistance mechanisms driving the adaptation of Cupriavidus metallidurans NA4 to toxic uranium concentrations. We selected a spontaneous mutant able to grow in the presence of 1 mM uranyl nitrate compared to 250 µM for the parental strain. The increased uranium resistance was acquired via the formation of periplasmic uranium-phosphate precipitates facilitated by the increased expression of a genus-specific small periplasmic protein, PrsQ2, regulated as non-cognate target of the CzcS2-CzcR2 two-component system. This study shows that bacteria can adapt to toxic uranium concentrations and explicates the complete genetic circuit behind the adaptation.

High incidence of clinical fragility fractures in postmenopausal women with rheumatoid arthritis. A case-control study.

OBJECTIVES: To estimate the incidence of clinical fragility fractures in postmenopausal women with rheumatoid arthritis (RA) and analyze risk factors for fracture. METHODS: Incidence of clinical fragility fractures in 330 postmenopausal women with RA was compared to that of a control population of 660 age-matched postmenopausal Spanish women. Clinical fractures during the previous five years were recorded. We analyzed associations with risk factors for fracture in both populations and with disease-related variables in RA patients. RESULTS: Median age of RA patients was 64 years; median RA duration was eight years. Sixty-nine percent were in remission or on low activity. Eighty-five percent had received glucocorticoids (GCs); 85 %, methotrexate; and 40 %, ≥1 biologic DMARD. Fifty-four patients and 47 controls had ≥1 major osteoporotic fracture (MOF). Incidence of MOFs was 3.55 per 100 patient-year in patients and 0.72 in controls (HR: 2.6). Risk factors for MOFs in RA patients were age, previous fracture, parental hip fracture, years since menopause, BMD, erosions, disease activity and disability, and cumulative dose of GCs. Previous fracture in RA patients was a strong risk for MOFs (HR: 10.37). CONCLUSION: Of every 100 postmenopausal Spanish women with RA, 3-4 have a MOF per year. This is more than double that of the general population. A previous fracture poses a high risk for a new fracture. Other classic risk factors for fracture, RA disease activity and disability, and the cumulative dose of GCs are associated with fracture development.

Characterization of glycoside hydrolase family 5 proteins in Schizosaccharomyces pombe.

In yeast, enzymes with ß-glucanase activity are thought to be necessary in morphogenetic events that require controlled hydrolysis of the cell wall. Comparison of the sequence of the Saccharomyces cerevisiae exo-ß(1,3)-glucanase Exg1 with the Schizosaccharomyces pombe genome allowed the identification of three genes that were named exg1(+) (locus SPBC1105.05), exg2(+) (SPAC12B10.11), and exg3(+) (SPBC2D10.05). The three proteins have different localizations: Exg1 is secreted to the periplasmic space, Exg2 is a membrane protein, and Exg3 is a cytoplasmic protein. Characterization of the biochemical activity of the proteins indicated that Exg1 and Exg3 are active only against ß(1,6)-glucans while no activity was detected for Exg2. Interestingly, Exg1 cleaves the glucans with an endohydrolytic mode of action. exg1(+) showed periodic expression during the cell cycle, with a maximum coinciding with the septation process, and its expression was dependent on the transcription factor Sep1. The Exg1 protein localizes to the septum region in a pattern that was different from that of the endo-ß(1,3)-glucanase Eng1. Overexpression of Exg2 resulted in an increase in cell wall material at the poles and in the septum, but the putative catalytic activity of the protein was not required for this effect.

Eng2, a new player involved in feedback loop regulation of Cdc42 activity in fission yeast.

Cell polarity and morphogenesis are regulated by the small GTPase Cdc42. Even though major advances have been done in the field during the last years, the molecular details leading to its activation in particular cellular contexts are not completely understood. In fission yeast, the ß(1,3)-glucanase Eng2 is a "moonlighting protein" with a dual function, acting as a hydrolase during spore dehiscence, and as component of the endocytic machinery in vegetative cells. Here, we report that Eng2 plays a role in Cdc42 activation during polarized growth through its interaction with the scaffold protein Scd2, which brings Cdc42 together with its guanine nucleotide exchange factor (GEF) Scd1. eng2Δ mutant cells have defects in activation of the bipolar growth (NETO), remaining monopolar during all the cell cycle. In the absence of Eng2 the accumulation of Scd1 and Scd2 at the poles is reduced, the levels of Cdc42 activation decrease, and the Cdc42 oscillatory behavior, associated with bipolar growth in wild type cells, is altered. Furthermore, overexpression of Eng2 partially rescues the growth and polarity defects of a cdc42-L160S mutant. Altogether, our work unveils a new factor regulating the activity of Cdc42, which could potentially link the polarity and endocytic machineries.

{beta}-glucanase Eng2 is required for ascus wall endolysis after sporulation in the fission yeast Schizosaccharomyces pombe.

Meiosis is the developmental program by which sexually reproducing diploid organisms generate haploid gametes. In yeast, meiosis is followed by spore morphogenesis. When Schizosaccharomyces pombe diploid cells undergo meiosis, they differentiate into asci containing four haploid ascospores that are highly resistant to environmental stress. The formation of the ascospore wall requires the activity of several enzymes involved in the biosynthesis and modification of its components, such as alpha- and beta-glucan synthases. Once the spores are completely mature, the wall of the ascus undergoes an endolytic process that results in the release of ascospores from the ascus, allowing their dispersal into the environment. This process requires the activity of the endo-alpha-1,3-glucanase Agn2. Here, we focus on the characterization of the endo-beta-1,3-glucanase Eng2, which is also required for ascospore release from the ascus. Although Eng2 is present during the mitotic cycle, the protein accumulates after meiosis II. The expression of eng2(+) is required for the efficient release of ascospores, as shown by placing eng2(+) under the control of a repressible promoter. Furthermore, a point mutation that destroys the catalytic activity of the protein results in a phenotype similar to that of the mutant strain. Finally, we demonstrate that exogenous addition of purified Eng2 releases the ascospores from asci generated by an eng2Delta mutant. We propose that Eng2 would act together with Agn2 to completely hydrolyze the ascus wall, thereby assisting in the release of ascospores in S. pombe.

The beta-1,3-glucanosyltransferase gas4p is essential for ascospore wall maturation and spore viability in Schizosaccharomyces pombe.

Meiosis is the developmental programme by which sexually reproducing diploid organisms generate haploid gametes. In yeast, meiosis is followed by spore morphogenesis. The formation of the Schizosaccharomyces pombe ascospore wall requires the co-ordinated activity of enzymes involved in the biosynthesis and modification of its components, such as glucans. During sporogenesis, the beta-1,3-glucan synthase bgs2p synthesizes linear beta-1,3-glucans, which remain unorganized and alkali-soluble until covalent linkages are set up between beta-1,3-glucans and other cell wall components. Several proteins belonging to the glycoside hydrolase family 72 (GH72) with beta-1,3-glucanosyltransferase activity have been described in other organisms, such as the Saccharomyces cerevisiae Gas1p or the Aspergillus fumigatus Gel1p. Here we describe the characterization of gas4(+), a new gene that encodes a protein of the GH72 family. Deletion of this gene does not lead to any apparent defect during vegetative growth, but homozygous gas4Delta diploids show a sporulation defect. Although meiosis occurs normally, ascospores are unable to mature or to germinate. The expression of gas4(+) is strongly induced during sporulation and a yellow fluorescent protein (YFP)-gas4p fusion protein localizes to the ascospore periphery during sporulation. We conclude that gas4p is required for ascospore maturation in S. pombe.

The Schizosaccharomyces pombe endo-1,3-beta-glucanase Eng1 contains a novel carbohydrate binding module required for septum localization.

Cell separation in Schizosaccharomyces pombe is achieved through the concerted action of the Eng1 endo-beta-1,3-glucanase and the Agn1 endo-alpha-1,3-glucanase, which are transported to the septum and localize to a ring-like structure that surrounds the septum. Correct localization of these hydrolases requires the presence of both the septins and the exocyst. In this work, we show that the glucanase Eng1 contains a region at the C-terminus that acts as a carbohydrate-binding module (CBM) and that it is not present in other members of glycoside hydrolases family 81 (GH81). In vitro, the purified CBM has affinity for beta-1,3-glucan chains with a minimum degree of polymerization of 30 glucose units. Deletion of the CBM results in a protein that is largely defective in complementing the separation defect of eng1Delta mutants. This defect is due to a reduction in the catalytic activity against insoluble substrates and to a defect in targeting of Eng1 to the septum, as the truncated protein localizes to the lateral cell wall of the cell. Thus, the targeting of Eng1 to the primary septum requires not only trans-factors (septins and the exocyst complex) but also a cis-element localized to the C-terminus of the protein.

A new toolkit for gene tagging in Candida albicans containing recyclable markers.

Gene manipulation and epitope tagging are essential tools for understanding the molecular function of specific genes. The opportunistic human pathogen Candida albicans is a diploid fungus that utilizes a non-canonical genetic code. Since selection markers available in this organism are scarce, several tools based on recyclable markers have been developed for gene disruption, such as the Clox system. This system relies on the Cre recombinase, which recycles selection markers flanked by loxP sites with high efficiency, facilitating single marker or multi-marker recycling. However, PCR-based modules for epitope tagging, such the pFA-modules, mainly use limited non-recyclable auxotrophic markers. To solve this problem, we have used a Gibson assembly strategy to construct a set of new plasmids where the auxotrophic markers of the pFA vectors were swapped with five recyclable marker modules of the Clox system, enhancing the versatility of the pFA plasmids. This new toolkit, named pFA-Clox, is composed of 36 new vectors for gene disruption and epitope tagging (GFP, 3xGFP, mCherry, 3xHA, 5xmyc and TAP). These plasmids contain the dominant NAT1 marker, as well as URA3, HIS1 and ARG4 cassettes, thereby permitting functional analysis of laboratory strains as well as clinical isolates of C. albicans. In summary, we have adapted the Clox system to the pFA-backbone vectors. Thus, the set of primers used for the amplification of previously published pFA modules can also be utilized in this new pFA-Clox system. Therefore, this new toolkit harbors the advantages of both systems, allowing accelerated gene modification strategies that could reduce time and costs in strain construction for C. albicans.

Septins localize to microtubules during nutritional limitation in Saccharomyces cerevisiae.

BACKGROUND: In Saccharomyces cerevisiae, nutrient limitation stimulates diploid cells to undergo DNA replication and meiosis, followed by the formation of four haploid spores. Septins are a family of proteins that assemble a ring structure at the mother-daughter neck during vegetative growth, where they control cytokinesis. In sporulating cells, the septin ring disassembles and septins relocalize to the prospore membrane. RESULTS: Here, we demonstrate that nutrient limitation triggers a change in the localization of at least two vegetative septins (Cdc10 and Cdc11) from the bud neck to the microtubules. The association of Cdc10 and Cdc11 with microtubules persists into meiosis, and they are found associated with the meiotic spindle until the end of meiosis II. In addition, the meiosis-specific septin Spr28 displays similar behavior, suggesting that this is a common feature of septins. Septin association to microtubules is a consequence of the nutrient limitation signal, since it is also observed when haploid cells are incubated in sporulation medium and when haploid or diploid cells are grown in medium containing non-fermentable carbon sources. Moreover, during meiosis II, when the nascent prospore membrane is formed, septins moved from the microtubules to this membrane. Proper organization of the septins on the membrane requires the sporulation-specific septins Spr3 and Spr28. CONCLUSION: Nutrient limitation in S. cerevisiae triggers the sporulation process, but it also induces the disassembly of the septin bud neck ring and relocalization of the septin subunits to the nucleus. Septins remain associated with microtubules during the meiotic divisions and later, during spore morphogenesis, they are detected associated to the nascent prospore membranes surrounding each nuclear lobe. Septin association to microtubules also occurs during growth in non-fermentable carbon sources.

Characterization of the endo-beta-1,3-glucanase activity of S. cerevisiae Eng2 and other members of the GH81 family.

The GH81 family includes proteins with endo-beta-1,3-glucanase widely distributed in yeast and fungi, which are also present in plants and bacteria. We have studied the activity of the Saccharomyces cerevisiae ScEng2 and the Schizosaccharomyces pombe SpEng1 and SpEng2 proteins. All three proteins exclusively hydrolyzed linear beta-1,3-glucan chains. Laminari-oligosaccharide degradation revealed that the minimum substrate length that the three endoglucanases were able to efficiently degrade was a molecule with at least 5 glucose residues, suggesting that the active site of the enzymes recognized five glucose units. Prediction of the secondary structure of ScEng2 and comparison with proteins of known structure allowed the identification of a 404-amino acid region with a structure similar to the Clostridium thermocellum endoglucanase CelA. This fragment showed similar enzymatic characteristics to those of the complete protein, suggesting that it contains the catalytic domain of this family of proteins. Within this domain, four conserved Asp and Glu residues (D518, D588, E609, and E613) are necessary for enzymatic activity.

Cdc15 is required for spore morphogenesis independently of Cdc14 in Saccharomyces cerevisiae.

In Saccharomyces cerevisiae exit from mitosis requires the Cdc14 phosphatase to reverse CDK-mediated phosphorylation. Cdc14 is released from the nucleolus by the Cdc14 early anaphase release (FEAR) and mitotic exit network (MEN) pathways. In meiosis, the FEAR pathway is essential for exit from anaphase I. The MEN component Cdc15 is required for the formation of mature spores. To analyze the role of Cdc15 during sporulation, a conditional mutant in which CDC15 expression was controlled by the CLB2 promoter was used. Cdc15-depleted cells proceeded normally through the meiotic divisions but were unable to properly disassemble meiosis II spindles. The morphology of the prospore membrane was aberrant and failed to capture the nuclear lobes. Cdc15 was not required for Cdc14 release from the nucleoli, but it was essential to maintain Cdc14 released and for its nucleo-cytoplasmic transport. However, cells carrying a CDC14 allele with defects in nuclear export (Cdc14-DeltaNES) were able to disassemble the spindle and to complete spore formation, suggesting that the Cdc14 nuclear export defect was not the cause of the phenotypes observed in cdc15 mutants.

Iodine supplementation during pregnancy: a public health challenge.

Iodine deficiency remains the most frequent cause worldwide, after starvation, of preventable mental retardation in children. It causes maternal hypothyroxinemia, which affects pregnant women even in apparently iodine-sufficient areas, and often goes unnoticed because L-thyroxine (T4) levels remain within the normal range, and thyroid-stimulating hormone (TSH) is not increased. Even a mild hypothyroxinemia during pregnancy increases the risk of neurodevelopmental abnormalities, and experimental data clearly demonstrate that it damages the cortical cytoarchitecture of the fetal brain. The American Thyroid Association (ATA) recommends a supplement of 150 microg iodine/day during pregnancy and lactation, in addition to the use of iodized salt. We discuss the importance of iodine supplementation to ensure adequate T4 levels in all women who are considering conception and throughout pregnancy and lactation.

Ace2p controls the expression of genes required for cell separation in Schizosaccharomyces pombe.

Schizosaccharomyces pombe cells divide by medial fission through contraction of an actomyosin ring and deposition of a multilayered division septum that must be cleaved to release the two daughter cells. Here we describe the identification of seven genes (adg1(+), adg2(+), adg3(+), cfh4(+), agn1(+), eng1(+), and mid2(+)) whose expression is induced by the transcription factor Ace2p. The expression of all of these genes varied during the cell cycle, maximum transcription being observed during septation. At least three of these proteins (Eng1p, Agn1p, and Cfh4p) localize to a ring-like structure that surrounds the septum region during cell separation. Deletion of the previously uncharacterized genes was not lethal to the cells, but produced defects or delays in cell separation to different extents. Electron microscopic observation of mutant cells indicated that the most severe defect is found in eng1Delta agn1Delta cells, lacking the Eng1p endo-beta-1,3-glucanase and the Agn1p endo-alpha-glucanase. The phenotype of this mutant closely resembled that of ace2Delta mutants, forming branched chains of cells. This suggests that these two proteins are the main activities required for cell separation to be completed.

Role of septins and the exocyst complex in the function of hydrolytic enzymes responsible for fission yeast cell separation.

Cell separation in Schizosaccharomyces pombe is achieved by the concerted action of the Eng1 endo-beta-1,3-glucanase and the Agn1 endo-alpha-1,3-glucanase, which are transported to the septum and localize to a ringlike structure that surrounds the septum. The requirements for the correct localization of both hydrolases as a ring were analyzed using green fluorescent protein fusion proteins. Targeting to the septum required a functional exocyst, because both proteins failed to localize correctly in sec8-1 or exo70delta mutants, suggesting that Agn1 and Eng1 might be two of the cargo proteins present in the vesicles that accumulate in exocyst mutants. Septins and Mid2 were also required for correct formation of a ring. In their absence, Eng1 and Agn1 were found in a disk-like structure that spanned the septum, rather than in a ring. Even though septin and mid2delta mutants have a cell separation defect, the septum and the distribution of linear beta-1,3-glucans were normal in these cells, suggesting that mislocalization of Eng1 and Agn1 might be the reason underlying the failure to separate efficiently. Thus, one of the functions of the septin ring would be to act as a positional marker for the localization of hydrolytic proteins to the medial region.

Epidemiology of osteoporotic fractures in Andalusia, Spain, from 2000-2010. / Epidemiología de las fracturas osteoporóticas en Andalucía en el período 2000-2010.

BACKGROUND AND OBJECTIVE: The aim of this study was to examine the epidemiological data on osteoporotic fractures in Andalusia in the period 2000-2010. In view of the lack of epidemiological studies of fractures in Andalusia, we set out to ascertain the number and incidence rates of osteoporotic fractures and their distribution by gender and age, location, comorbidity, seasonality and secular trend. METHODS: Cohort study observed over a period of 11 years analysing the data provided by the Minimum Basic Data Set register for the period 2000-2010. RESULTS: There were a total of 96,458 osteoporotic fractures, with a crude incidence rate of 374.18 fractures per 100,000 population. Fractures increased in this period by 27% (p<.01, IC 95%, 0.71; 0.73). We found a trend change in female/male ratio, from 3.4 to 3.2, and in the reduction in fractures in the last two years, especially in the past year, with a decrease of 11.2% in hip fractures (p<.001, IC 95%, 0.88; 0.895). CONCLUSIONS: In this period, there has been an increase in fractures as a consequence of the ageing of the population, but also a change in trend, with fractures decreasing in some age groups. The incidence rate of fractures varies between different countries and regions of Spain, and between different provinces of Andalusia.

The anillin-related Int1 protein and the Sep7 septin collaborate to maintain cellular ploidy in Candida albicans.

Variation in cell ploidy is a common feature of Candida albicans clinical isolates that are resistant to the antifungal drug fluconazole. Here, we report that the anillin-related protein Int1 interacts with septins for coupling cytokinesis with nuclear segregation. Loss of Int1 results in a rapid disassembly of duplicated septin rings from the bud neck at the onset of actomyosin ring contraction. Strikingly, this has no major impact on cytokinesis and septum formation. However, Int1 genetically interacts with the Sep7 septin, maintaining the diffusion barrier at the bud neck and guarantying a faithful nuclear segregation. Indeed, int1ΔΔ sep7ΔΔ mutant cells, in contrast to int1ΔΔ cdc10ΔΔ, undergo a premature activation of mitotic exit prior to the alignment of the mitotic spindle with the division axis, producing large multinucleated cells. Some of these multinucleated cells arise from trimeras similar to those observed upon fluconazole exposure. Finally, the defects in nuclear segregation could be in part due to the inability to maintain the Lte1 mitotic exit activator at the cortex of the daughter cell. These results suggest that Int1 and Sep7 play a role in maintaining genome stability by acting as a diffusion barrier for Lte1.