Centromeric DNA sequences in the pathogenic yeast
            <i>Candida albicans</i>
            are all different and unique

Sanyal, Kaustuv; Baum, Mary; Carbon, John

doi:10.1073/pnas.0404318101

Cited by 180 publications

(209 citation statements)

References 42 publications

(26 reference statements)

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“…Cse4 (orthologous to mammalian CENP-A) is a centromere-specific variant of histone H3, and Mif2 (orthologous to mammalian CENP-C) is an inner kinetochore component. Both proteins are associated with centromeres in other yeast species (13,23,35). We generated strains expressing myctagged alleles of Cse4 and Mif2 from the endogenous chromosomal loci, and these strains were used for ChIP-Seq.…”

Section: Resultsmentioning

confidence: 99%

“…In Candida albicans and Candida dubliniensis, Cse4/ CENP-A is associated with 3-5 kbp of DNA (22)(23)(24). This length is much greater than the point centromeres of S. cerevisiae but not as long as the 10-to 15-kbp centromeric core of S. pombe.…”

mentioning

confidence: 96%

“…This length is much greater than the point centromeres of S. cerevisiae but not as long as the 10-to 15-kbp centromeric core of S. pombe. C. albicans centromeric cores have no common sequence and are epigenetically inherited (23,25). However, it is not clear whether these centromeres are flanked by heterochromatin.…”

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confidence: 99%

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Regional centromeres in the yeast Candida lusitaniae lack pericentromeric heterochromatin

Kapoor

Zhu

Froyd

et al. 2015

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

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Point centromeres are specified by a short consensus sequence that seeds kinetochore formation, whereas regional centromeres lack a conserved sequence and instead are epigenetically inherited. Regional centromeres are generally flanked by heterochromatin that ensures high levels of cohesin and promotes faithful chromosome segregation. However, it is not known whether regional centromeres require pericentromeric heterochromatin. In the yeast Candida lusitaniae, we identified a distinct type of regional centromere that lacks pericentromeric heterochromatin. Centromere locations were determined by ChIP-sequencing of two key centromere proteins, Cse4 and Mif2, and are consistent with bioinformatic predictions. The centromeric DNA sequence was unique for each chromosome and spanned 4-4.5 kbp, consistent with regional epigenetically inherited centromeres. However, unlike other regional centromeres, there was no evidence of pericentromeric heterochromatin in C. lusitaniae. In particular, flanking genes were expressed at a similar level to the rest of the genome, and a URA3 reporter inserted adjacent to a centromere was not repressed. In addition, regions flanking the centromeric core were not associated with hypoacetylated histones or a sirtuin deacetylase that generates heterochromatin in other yeast. Interestingly, the centromeric chromatin had a distinct pattern of histone modifications, being enriched for methylated H3K79 and H3R2 but lacking methylation of H3K4, which is found at other regional centromeres. Thus, not all regional centromeres require flanking heterochromatin.centromere | heterochromatin | Candida | CSE4 | Sir2

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 96%

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Regional centromeres in the yeast Candida lusitaniae lack pericentromeric heterochromatin

Kapoor

Zhu

Froyd

et al. 2015

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

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“…Similar to S. cerevisiae, only one MT binds to a KT in C. albicans (25). C. albicans has 3-to 5-kb-long CENP-A-rich centromere sequences that are unique and different from each other on various chromosomes (3,43). The properties of C. albicans centromeres appear to be intermediate between those of S. cerevisiae (125-bp-long centromeres) and S. pombe (40-to 110-kb-long centromeres), thus C. albicans is a good system to study the functional evolution of the Dam1 complex.…”

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confidence: 99%

“…ChIP assays with anti-CENP-A antibodies were performed as described before (40,43). ChIP assays with anti-protein A antibodies in J117 (Dam1-Prot A) and J118 (Dad2-Prot A) strains were performed using the same protocol except for the following modifications: J117 cells were cross-linked with 1% formaldehyde for 90 min, while J118 cells were cross-linked for 120 min.…”

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confidence: 99%

The Essentiality of the Fungus-Specific Dam1 Complex Is Correlated with a One-Kinetochore-One-Microtubule Interaction Present throughout the Cell Cycle, Independent of the Nature of a Centromere

Thakur

Sanyal

2011

Eukaryot Cell

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A fungus-specific outer kinetochore complex, the Dam1 complex, is essential in Saccharomyces cerevisiae, nonessential in fission yeast, and absent from metazoans. The reason for the reductive evolution of the functionality of this complex remains unknown. Both Candida albicans and Schizosaccharomyces pombe have regional centromeres as opposed to the short-point centromeres of S. cerevisiae. The interaction of one microtubule per kinetochore is established both in S. cerevisiae and C. albicans early during the cell cycle, which is in contrast to the multiple microtubules that bind to a kinetochore only during mitosis in S. pombe. Moreover, the Dam1 complex is associated with the kinetochore throughout the cell cycle in S. cerevisiae and C. albicans but only during mitosis in S. pombe. Here, we show that the Dam1 complex is essential for viability and indispensable for proper mitotic chromosome segregation in C. albicans. The kinetochore localization of the Dam1 complex is independent of the kinetochoremicrotubule interaction, but the function of this complex is monitored by a spindle assembly checkpoint. Strikingly, the Dam1 complex is required to prevent precocious spindle elongation in premitotic phases. Thus, constitutive kinetochore localization associated with a one-microtubule-one kinetochore type of interaction, but not the length of a centromere, is correlated with the essentiality of the Dam1 complex.The separation of sister chromatids during mitosis is driven by a dynamic interaction between two macromolecular structures: (i) the kinetochore (KT), a complex proteinaceous structure built on the centromere DNA (10, 47), and (ii) the mitotic spindle formed by microtubules (MTs). The process of chromosome segregation has been studied extensively in a wide range of organisms, from simple unicellular yeasts to humans. While the major sequence of events required for chromosome segregation remains the same, a few species-specific differences exist. The microtubule organizing centers (MTOCs) in budding yeasts, called spindle pole bodies (SPBs), are embedded in the nuclear envelope and assemble an intranuclear mitotic spindle (5). Thus, the interaction of spindle MTs with KTs does not require the breakdown of the nuclear envelope during closed mitosis in budding yeasts, and the KT-MT interaction is established early in the cell cycle (12, 23). The fission yeast Saccharomyces pombe also undergoes closed mitosis (23), but SPBs remain outside the nuclear envelope during interphase (27) and spindle MTs are nucleated and interact with KTs only when the duplicated SPBs enter the nuclear membrane following mitotic initiation (14). Metazoan cells, in contrast, undergo open mitosis (22,45) in which the MTs, originating from MTOCs, gain access to KTs only when the nuclear envelope breaks down during mitosis. Finally, the number of MTs that bind to a single chromosome differs in these organisms: in Saccharomyces cerevisiae only one MT binds per KT (52), in S. pombe two or three MTs bind per KT (13), and in metazoans multipl...

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Epigenetics of Filamentous Fungi

Smith

Phatale

Bredeweg

et al. 2012

Encyclopedia of Molecular Cell Biology and Molecular Medicine

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Centromeric DNA sequences in the pathogenic yeast Candida albicans are all different and unique

Cited by 180 publications

References 42 publications

Regional centromeres in the yeast Candida lusitaniae lack pericentromeric heterochromatin

Regional centromeres in the yeast Candida lusitaniae lack pericentromeric heterochromatin

The Essentiality of the Fungus-Specific Dam1 Complex Is Correlated with a One-Kinetochore-One-Microtubule Interaction Present throughout the Cell Cycle, Independent of the Nature of a Centromere

Epigenetics of Filamentous Fungi

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