Candida albicans Cdc15 is essential for mitotic exit and cytokinesis

Bates, Steven

doi:10.1038/s41598-018-27157-y

Cited by 12 publications

(14 citation statements)

References 66 publications

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“…In contrast, pseudohyphal growth induced by nocodazole requires the spindle assembly checkpoint factor Mad2, but not its upstream kinase Mps1 ( Bai et al, 2002 ; Kamthan et al, 2014 ). Failure to exit mitosis by depleting cells of the kinase Cdc15 or the GTPase Tem1 that function in the mitotic exit network also results in filamentation, and this phenotype is terminal ( Bates, 2018 ; Milne et al, 2014 ). Altogether, this shows that checkpoint proteins play an integral role in faithful completion of the cell cycle and in filamentation in response to genotoxic stress ( Shapiro et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Functional connections between cell cycle and proteostasis in the regulation of Candida albicans morphogenesis

et al. 2021

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SUMMARY Morphological plasticity is a key virulence trait for many fungal pathogens. For the opportunistic fungal pathogen Candida albicans , transitions among yeast, pseudohyphal, and hyphal forms are critical for virulence, because the morphotypes play distinct roles in the infection process. C. albicans morphogenesis is induced in response to many host-relevant conditions and is regulated by complex signaling pathways and cellular processes. Perturbation of either cell-cycle progression or protein homeostasis induces C. albicans filamentation, demonstrating that these processes play a key role in morphogenetic control. Regulators such as cyclin-dependent kinases, checkpoint proteins, the proteasome, the heat shock protein Hsp90, and the heat shock transcription factor Hsf1 all influence morphogenesis, often through interconnected effects on the cell cycle and proteostasis. This review highlights the major cell-cycle and proteostasis regulators that modulate morphogenesis and discusses how these two processes intersect to regulate this key virulence trait.

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Section: Introductionmentioning

confidence: 99%

Functional connections between cell cycle and proteostasis in the regulation of Candida albicans morphogenesis

et al. 2021

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“…, 2010; Weiss 2012). In C. albicans, these pathways are not well defined (Bates, 2018). Further, C. albicans homologues of some S. cerevisiae MEN factors, including Dbf2p and Cdc14p, have prominent functions in additional processes (Clemente-Blanco et al.…”

Section: Discussionmentioning

confidence: 99%

“…For example, several C. albicans homologues of MEN factors are required for mitotic exit in a manner similar to the situation in S. cerevisiae (Milne et al. , 2014; Bates, 2018; Orellana-Muñoz et al. , 2018), but others have additional functions (Clemente-Blanco et al.…”

Section: Introductionmentioning

confidence: 99%

Characterization of a novel separase-interacting protein and candidate new securin, Eip1p, in the fungal pathogen Candida albicans

Sparapani

Bachewich

2019

MBoC

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Proper chromosome segregation is crucial for maintaining genomic stability and dependent on separase, a conserved and essential cohesin protease. Securins are key regulators of separases, but remain elusive in many organisms due to sequence divergence. Here, we demonstrate that the separase homologue Esp1p in the ascomycete Candida albicans, an important pathogen of humans, is essential for chromosome segregation . However, C. albicans lacks a sequence homologue of securins found in model ascomycetes. We sought a functional homologue through identifying Esp1p interacting factors. Affinity purification of Esp1p and mass spectrometry revealed Esp1p-Interacting Protein1 (Eip1p)/Orf19.955p, an uncharacterized protein specific to Candida species. Functional analyses demonstrated that Eip1p is important for chromosome segregation but not essential, and modulated in an APCCdc20-dependent manner, similar to securins. Eip1p is strongly enriched in response to methyl methanesulfate (MMS) or hydroxyurea (HU) treatment, and its depletion partially suppresses an MMS or HU-induced metaphase block. Further, Eip1p depletion reduces Mcd1p/Scc1p, a cohesin subunit and separase target. Thus, Eip1p may function as a securin. However, other defects in Eip1p-depleted cells suggest additional roles. Overall, the results introduce a candidate new securin, provide an approach for identifying these divergent proteins, reveal a putative anti-fungal therapeutic target, and highlight variations in mitotic regulation in eukaryotes.

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“…CAKS3b (Sanyal and Carbon 2002) was grown in YP with succinate (2%) for expressing CENPA and in YP with dextrose (2%) for depleting CENPA for 8 h. SC5314 was grown in YPDU. The cdc15 mutant SBC189 (Bates 2018) was grown in CM and repressed in presence of 20 μg/mL doxycycline for 16 h. To arrest cells in the S phase, YJB8675 (Joglekar et al 2008)…”

Section: Media and Growth Conditionsmentioning

confidence: 99%

Orc4 spatiotemporally stabilizes centromeric chromatin

et al. 2021

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The establishment of centromeric chromatin and its propagation by the centromere-specific histone CENPA is mediated by epigenetic mechanisms in most eukaryotes. DNA replication origins, origin binding proteins, and replication timing of centromere DNA are important determinants of centromere function. The epigenetically regulated regional centromeres in the budding yeast Candida albicans have unique DNA sequences that replicate earliest in every chromosome and are clustered throughout the cell cycle. In this study, the genome-wide occupancy of the replication initiation protein Orc4 reveals its abundance at all centromeres in C. albicans. Orc4 is associated with four different DNA sequence motifs, one of which coincides with tRNA genes (tDNA) that replicate early and cluster together in space. Hi-C combined with genome-wide replication timing analyses identify that early replicating Orc4-bound regions interact with themselves stronger than with late replicating Orc4-bound regions. We simulate a polymer model of chromosomes of C. albicans and propose that the early replicating and highly enriched Orc4-bound sites preferentially localize around the clustered kinetochores. We also observe that Orc4 is constitutively localized to centromeres, and both Orc4 and the helicase Mcm2 are essential for cell viability and CENPA stability in C. albicans. Finally, we show that new molecules of CENPA are recruited to centromeres during late anaphase/telophase, which coincides with the stage at which the CENPA-specific chaperone Scm3 localizes to the kinetochore. We propose that the spatiotemporal localization of Orc4 within the nucleus, in collaboration with Mcm2 and Scm3, maintains centromeric chromatin stability and CENPA recruitment in C. albicans.

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Candida albicans Cdc15 is essential for mitotic exit and cytokinesis

Cited by 12 publications

References 66 publications

Functional connections between cell cycle and proteostasis in the regulation of Candida albicans morphogenesis

Functional connections between cell cycle and proteostasis in the regulation of Candida albicans morphogenesis

Characterization of a novel separase-interacting protein and candidate new securin, Eip1p, in the fungal pathogen Candida albicans

Orc4 spatiotemporally stabilizes centromeric chromatin

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