Rad52 depletion in <i>Candida albicans</i> triggers both the DNA‐damage checkpoint and filamentation accompanied by but independent of expression of hypha‐specific genes

Andaluz, Encarnación; Ciudad, Toni; Gómez-Raja, Jonathan; Calderone, Richard; Larriba, Germán

doi:10.1111/j.1365-2958.2005.05038.x

Cited by 68 publications

(96 citation statements)

References 76 publications

(110 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In contrast to the colony and cell morphology phenotypes exhibited by double-strand-break repair mutants (Andaluz et al, 2006;Legrand et al, 2007), including strains derived from the same parental background as used in this study, the mutants grew like wild-type yeast cells in liquid cultures at 30 u C (data not shown). We characterized the growth rates of the deletion mutant strains and observed that the BER and NER mutants had a doubling time similar to that of the parental strain (Table 4).…”

Section: Gene Disruption and Phenotypic Analysismentioning

confidence: 47%

Analysis of base excision and nucleotide excision repair in Candida albicans

et al. 2008

View full text Add to dashboard Cite

Candida albicans, clinically the most important human fungal pathogen, rapidly develops resistance to antifungal drugs. The acquisition of resistance has been linked to various types of genome changes. As part of an ongoing study of this problem, we investigated mutation, genome stability and drug resistance acquisition in C. albicans strains with deletions in the base excision repair (BER) genes NTG1, APN1 and OGG1, and in the nucleotide excision repair (NER) genes RAD2 and RAD10. The BER mutants did not exhibit any change in their susceptibility to DNA-damaging agents, but the NER mutants were extremely sensitive to UV-induced DNA damage. We did not observe any significant change in mutation, genome stability and antifungal drug sensitivity in the mutant strains we tested. However, we detected a number of intriguing phenotypic differences between strains bearing deletions in equivalent C. albicans and Saccharomyces cerevisiae BER and NER genes, which may be related to differences in the life cycles of these two fungi.

show abstract

Section: Gene Disruption and Phenotypic Analysismentioning

confidence: 47%

Analysis of base excision and nucleotide excision repair in Candida albicans

et al. 2008

View full text Add to dashboard Cite

show abstract

“…The ability to switch among these morphologies is required for C. albicans pathogenicity (38,39), suggesting that multiple morphologies contribute to host infection. Filamentous growth can be triggered by various stimuli, including oxidative stress (40), activation of the DNA damage, and replication checkpoints due to exogenous or endogenous DNA damage (41,42), or by cell-cycle delays resulting from perturbed microtubule dynamics or spindle checkpoint activation (43,44; reviewed in ref. 45).…”

Section: Resultsmentioning

confidence: 99%

Histone acetyltransferase Rtt109 is required for Candida albicans pathogenesis

Rosa

Boyartchuk

Zhu

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

123

127

View full text Add to dashboard Cite

Candida albicans is a ubiquitous opportunistic pathogen that is the most prevalent cause of hospital-acquired fungal infections. In mammalian hosts, C. albicans is engulfed by phagocytes that attack the pathogen with DNA-damaging reactive oxygen species (ROS). Acetylation of histone H3 lysine 56 (H3K56) by the fungal-specific histone acetyltransferase Rtt109 is important for yeast model organisms to survive DNA damage and maintain genome integrity. To assess the importance of Rtt109 for C. albicans pathogenicity, we deleted the predicted homolog of Rtt109 in the clinical C. albicans isolate, SC5314. C. albicans rtt109 −/− mutant cells lack acetylated H3K56 (H3K56ac) and are hypersensitive to genotoxic agents. Additionally, rtt109 −/− mutant cells constitutively display increased H2A S129 phosphorylation and elevated DNA repair gene expression, consistent with endogenous DNA damage. Importantly, C. albicans rtt109 −/− cells are significantly less pathogenic in mice and more susceptible to killing by macrophages in vitro than are wild-type cells. Via pharmacological inhibition of the host NADPH oxidase enzyme, we show that the increased sensitivity of rtt109 −/− cells to macrophages depends on the host's ability to generate ROS, providing a mechanistic link between the drug sensitivity, gene expression, and pathogenesis phenotypes. We conclude that Rtt109 is particularly important for fungal pathogenicity, suggesting a unique target for therapeutic antifungal compounds.acetylation | chromatin | fungal pathogenesis | DNA damage resistance | macrophage

show abstract

“…These conditions more-or-less mimic certain host conditions. Interestingly, recent experiments have revealed a seemingly new mechanism for induction of filamentous growth that is caused by the perturbation of cell-cycle progression and is, in at least some cases, independent of the cAMP/PKA and MAP-kinase pathways (Bai et al, 2002;Bachewich et al, 2003;Andaluz et al, 2006; AtirLande et al, 2005;Bensen et al, 2005;Chapa y Lazo et al, 2005). An intriguing observation is that interfering with either an early or a late cell-cycle event, or with events thought to activate distinct cell-cycle checkpoints, appears to have strikingly similar effects on cell morphogenesis.…”

Section: Introductionmentioning

confidence: 99%

“…In C. albicans, the spindle-assembly checkpoint was shown to be required for nocodazole-induced filamentous growth (Bai et al, 2002). Recently, Andaluz et al (2006) reported that Rad52p depletion triggers the DNA-damage checkpoint and constitutive filamentation. These observations raise the important question of whether the cell-cycle checkpoints may play active roles in promoting filamentous growth under conditions that perturb cell-cycle progression.…”

mentioning

confidence: 99%

Critical Role of DNA Checkpoints in Mediating Genotoxic-Stress–induced Filamentous Growth inCandida albicans

Shi

Wang

Zheng

et al. 2007

MBoC

115

198

View full text Add to dashboard Cite

The polymorphic fungus Candida albicans switches from yeast to filamentous growth in response to a range of genotoxic insults, including inhibition of DNA synthesis by hydroxyurea (HU) or aphidicolin (AC), depletion of the ribonucleotidereductase subunit Rnr2p, and DNA damage induced by methylmethane sulfonate (MMS) or UV light (UV). Deleting RAD53, which encodes a downstream effector kinase for both the DNA-replication and DNA-damage checkpoint pathways, completely abolished the filamentous growth caused by all the genotoxins tested. Deleting RAD9, which encodes a signal transducer of the DNA-damage checkpoint, specifically blocked the filamentous growth induced by MMS or UV but not that induced by HU or AC. Deleting MRC1, the counterpart of RAD9 in the DNA-replication checkpoint, impaired DNA synthesis and caused cell elongation even in the absence of external genotoxic insults. Together, the results indicate that the DNA-replication/damage checkpoints are critically required for the induction of filamentous growth by genotoxic stress. In addition, either of two mutations in the FHA1 domain of Rad53p, G65A, and N104A, nearly completely blocked the filamentous-growth response but had no significant deleterious effect on cell-cycle arrest. These results suggest that the FHA domain, known for its ability to bind phosphopeptides, has an important role in mediating genotoxic-stress-induced filamentous growth and that such growth is a specific, Rad53p-regulated cellular response in C. albicans. INTRODUCTIONThe polymorphic fungus Candida albicans has proven to be a very useful model for the study of cell morphogenesis (Odds, 1994;Sudbery et al., 2004;Wightman et al., 2004;Zheng et al., 2004). This organism can switch between several morphological forms including yeast, pseudohyphae, and hyphae (Berman and Sudbery, 2002;Sudbery et al., 2004). The yeast-hypha transition has attracted much attention because of its established importance for infection and virulence (Csank et al., 1997;Lo et al., 1997;Gale et al., 1998;Gow et al., 2002;Zheng et al., 2004). Several signal-transduction pathways are known to play roles in growth-form selection (Liu, 2001;Berman and Sudbery, 2002). The cAMPprotein kinase A (PKA) pathway has a key role, because blocking it abolishes true hyphal growth under most experimental conditions (Lo et al., 1997;Stoldt et al., 1997;Rocha et al., 2001). Another important pathway contains a MAPkinase cascade that seems to have a more important role in regulating pseudohyphal than true hyphal growth (Liu et al., 1994). The two pathways control the transcription factors Efg1p and Cph1p, respectively, which activate the expression of hypha-specific genes for a suite of infection-related functions (Lane et al., 2001).A diverse range of environmental stimuli can induce C. albicans hyphal or pseudohyphal growth, such as serum, neutral pH, appropriate temperature, certain amino acids and sugars, and some synthetic growth media (Ernst, 2000;Sudbery et al., 2004). These conditions more-or-less mimic certain host c...

show abstract

Rad52 depletion in Candida albicans triggers both the DNA‐damage checkpoint and filamentation accompanied by but independent of expression of hypha‐specific genes

Cited by 68 publications

References 76 publications

Analysis of base excision and nucleotide excision repair in Candida albicans

Analysis of base excision and nucleotide excision repair in Candida albicans

Histone acetyltransferase Rtt109 is required for Candida albicans pathogenesis

Critical Role of DNA Checkpoints in Mediating Genotoxic-Stress–induced Filamentous Growth inCandida albicans

Contact Info

Product

Resources

About