Pdd1p, A Novel Chromodomain-Containing Protein, Links Heterochromatin Assembly and DNA Elimination in Tetrahymena

Madireddi, Malavi T.; Coyne, Robert S.; Smothers, James; Mickey, Katherine M.; Yao, Meng-Chao; Allis, C. David

doi:10.1016/s0092-8674(00)81324-0

Cited by 164 publications

(209 citation statements)

References 69 publications

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“…However, little is known about how the deletion-rejoining associated with IESs and the breakageresection-telomere addition associated with BESs are performed during the later stages of elimination. Pdd proteins are essential for DNA elimination, can be coimmunoprecipitated with IESs, and colocalize with them in subnuclear organelles (DNA elimination structures) in developing MACs (20,33). Thus, an understanding of the biogenesis and composition of elimination structures is likely to shed light on the later stages of DNA elimination.…”

Section: Discussionmentioning

confidence: 99%

Centromeric Histone H3 Is Essential for Vegetative Cell Division and for DNA Elimination during Conjugation in Tetrahymena thermophila

Cui

Gorovsky

2006

Molecular and Cellular Biology

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The Tetrahymena thermophila CNA1 gene encodes the centromeric H3, Cna1p. Green fluorescent protein (GFP)-tagged Cna1p localizes in micronuclei in dots whose number and behavior during mitosis and conjugation are consistent with centromeres. During interphase, Cna1p-GFP localizes in peripheral dots, suggesting centromeres are associated with the nuclear envelope. Newly synthesized Cna1p-GFP enters micronuclei in mitosis and accumulates in the nucleoplasm. Its deposition at centromeres starts at early S phase and continues through most of S phase. CNA1 is required for vegetative cell growth. Knockdown of CNA1 genes in the somatic macronucleus results in micronuclear DNA loss and delayed chromosome segregation during mitosis. During conjugation, Cna1p-GFP disappears from the centromeres in the developing macronucleus, consistent with centromeric sequences being internal eliminated sequences. Surprisingly, zygotic CNA1 is required for efficient elimination of germ line-specific sequences during development of the new macronuclei but not for the RNA interference pathway, through which sequences are targeted for elimination. Zygotically expressed Cna1p localizes in the spherical structures in which the later stages of DNA elimination occur, and these structures cannot be formed in the absence of zygotic CNA1, suggesting that, in addition to functioning in centromeres, Cna1p may also play a role in organizing the formation of the DNA elimination structures.

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Section: Discussionmentioning

confidence: 99%

Centromeric Histone H3 Is Essential for Vegetative Cell Division and for DNA Elimination during Conjugation in Tetrahymena thermophila

Cui

Gorovsky

2006

Molecular and Cellular Biology

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“…50 Interestingly, in the ciliates Tetrahymena and Stylonychia, two homologous nucleases (Pdd1p and Spdd1p, respectively), with a size of 54 kDa, were described as being implicated in the apoptotic-like degradation of the nuclei. 8,30 To date, there has been no description of such nucleases in trypanosomatids. The only nuclease with similar size (although a bit smaller, 43 kDa) that was described in Leishmania is the surface 3'-nucleotidase/nuclease.…”

Section: Discussionmentioning

confidence: 99%

“…25,29 In Tetrahymena and in Stylonychia, morphological changes and proteins possibly involved in programmed DNA degradation have been described. 8,12,30 However, none of these reports provide answers about the implicated pathways except in the case of death in Trypanosoma brucei, which was shown to be Ca 2+ -dependent when induced by reactive oxygen species (ROS). In this case, however, parasites expressing mouse Bcl-2 were not protected from ROS even though protection from mitochondrial dysfunction and ROS have been reported for mammalian cells.…”

Section: Introductionmentioning

confidence: 99%

Cell death in Leishmania induced by stress and differentiation: programmed cell death or necrosis?

2002

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Unicellular organisms, such as the protozoan parasite Leishmania, can be stimulated to show some morphological and biochemical features characteristic of mammalian apoptosis. This study demonstrates that under a variety of stress conditions such as serum deprivation, heat shock and nitric oxide, cell death can be induced leading to genomic DNA fragmentation into oligonucleosomes. DNA fragmentation was observed, without induction, in the infectious stages of the parasite, and correlated with the presence of internucleosomal nuclease activity, visualisation of 45 to 59 kDa nucleases and detection of TUNEL-positive nuclei. DNA fragmentation was not dependent on active effector downstream caspases nor on the lysosomal cathepsin L-like enyzmes CPA and CPB. These data are consistent with the presence of a caspase-independent cell death mechanism in Leishmania, induced by stress and differentiation that differs significantly from metazoa.

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“…Other roles for RNA-directed rewriting of DNA have been discovered in tetrahymena. This organism has two nuclei: a germline micronucleus that is transmitted to progeny and a somatic macronucleus that is actively transcribed [76][77][78] . The macronucleus is created from the micronucleus.…”

Section: Rna-directed Rewriting Of Dnamentioning

confidence: 99%

“…The macronucleus is created from the micronucleus. During this process, the deletion of DNA sequences is guided by homologous RNA transcripts from the micronucleus [76][77][78] . New sequences appearing in the macronucleus during one reproductive cycle are targeted for deletion in the next generation, ensuring, for example, that the genome is not destabilized by the spread of DNA transposons 78 .…”

Section: Rna-directed Rewriting Of Dnamentioning

confidence: 99%

The four Rs of RNA-directed evolution

Herbert

2003

Nat Genet

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The read-out of genetic information in eukaryotes is not only more complex than previously realized, but also more dynamic. Much of the information is 'soft-wired' , with extensive RNA processing necessary to generate phenotypes 10 . A subset of the RNA, referred to here as coRNA ( Fig. 1), coordinates the read-out of genetic information and reconciles regulatory inputs. For each cell type, the sum of these interactions defines a distinct RNA profile or ribotype 10 . RNA-based processes also facilitate replication of ribotypes in subsequent generations. The flexibility of these programs allows soft-wired organisms to evolve in a more rapid and dynamic way than 'hard-wired' organisms constrained by DNA mutation 10 . Together, the actions of reading, 'riting, 'rithmetic and replication constitute the four Rs of RNA-directed evolution. Here, we describe roles for coRNAs and SATs (Fig. 2) in these events. RNA-directed RNA readoutRNA coregulates the sequence-specific read-out of genetic information from RNA by targeting the evolutionarily conserved machinery of RNA interference (RNAi) 11 and translational repression. RNAi leading to post-transcriptional gene silencing (PTGS) is induced by doublestranded RNA (dsRNA) arising from infection by dsRNA viruses, senseantisense transcription pairs, transcription of inverted repeats and delivery of dsRNAs manufactured in vitro 12 . Both endogenous and exogenous dsRNAs are processed cytoplasmically by RNase III dicer paralogs into small interfering RNAs (siRNAs) that are 21-25 bases long 12,13 . These siRNAs are incorporated into an RNA-induced silencing complex (RISC) that targets any RNA with a sequence complementary to the siRNA 12,14 . The target RNA is cleaved by RISC, which has endonucleolytic and presumed exonucleolytic activity 12,15 . Each cycle results in the destruction of the target RNA and the regeneration of an active RISC 16,17 .In Neurospora crassa 18,19 , plants 20 , Schizosaccharomyces pombe 21 and Caenorhabditis elegans 22 , but not in flies, humans or mouse oocyctes 18,19,23,24 , PTGS can also be initiated by an RNA-dependent RNA polymerase (RdRP) that synthesizes complementary RNA from highly expressed transcripts to generate dsRNA. This process can spread from the 3´ to the 5´ end of the mRNA, leading to progressive silencing of a gene and other mRNAs with exons in common (transitive RNAi) 18,22 . From the evolutionary viewpoint, transitive RNAi favors the generation of new phenotypes, as related genes in species with polyploid genomes will escape cosuppression by sequence divergence, resulting in altered function or expression.The number of dicer paralogs also differs between species. Arabidopsis, which has at least four dicer family members, seems to use different enzymes to defend against viruses and to process endogenously produced dsRNA 13,25 . In humans, mice and worms, there is only one dicer ortholog, suggesting that any pathway-specific functions are guided by ancillary regulatory proteins associated with RISC. These ancillary proteins include me...

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Pdd1p, A Novel Chromodomain-Containing Protein, Links Heterochromatin Assembly and DNA Elimination in Tetrahymena

Cited by 164 publications

References 69 publications

Centromeric Histone H3 Is Essential for Vegetative Cell Division and for DNA Elimination during Conjugation in Tetrahymena thermophila

Centromeric Histone H3 Is Essential for Vegetative Cell Division and for DNA Elimination during Conjugation in Tetrahymena thermophila

Cell death in Leishmania induced by stress and differentiation: programmed cell death or necrosis?

The four Rs of RNA-directed evolution

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