Impaired cohesion and homologous recombination during replicative aging in budding yeast

Pal, Sangita; Postnikoff, Spike D. L.; Chavez, Myrriah; Tyler, Jessica K.

doi:10.1126/sciadv.aaq0236

Cited by 43 publications

(62 citation statements)

References 55 publications

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“…with an independent study that analyzed significantly older mother cells (~25 generations) and observed reduced cohesin enrichment at centromeres and severe loss of SCC (PAL et al 2018). 632…”

Section: Nuclear Protein Depletion During Replicative Aging As a Paramentioning

confidence: 90%

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Depletion of limiting rDNA structural complexes triggers chromosomal instability and replicative aging ofSaccharomyces cerevisiae

Fine

Maqani

et al. 2018

Preprint

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20Sir2 is a highly conserved NAD + -dependent histone deacetylase that functions in 21 heterochromatin formation and promotes replicative lifespan (RLS) in the budding yeast, 22Saccharomyces cerevisiae. Within the yeast rDNA locus, Sir2 is required for efficient cohesin 23 recruitment and maintaining stability of the tandem array. In addition to the rDNA, ChIP-seq of 24 an epitope-tagged cohesin subunit (Mcd1-13xMyc) in a sir2∆ mutant revealed subtle reductions 25 of cohesin binding at all 16 centromeres. Coupled with the previously reported chromosome 26 instability in sir2∆ cells and depletion of Sir2 in aged cells, we hypothesized that mitotic 27 chromosome instability (CIN) due to Sir2 depletion could be a driver of replicative aging. In 28 addition to Sir2, we discovered that other subunits of the Sir2-containing SIR and RENT 29 complexes were depleted in aged cells, as were subunits of the cohesin and monopolin/cohibin 30 complexes, implying the possibility of CIN. ChIP assays of the residual Mcd1-13xMyc in aged 31 cells showed strong depletion from the rDNA and possible redistribution to centromeres, most 32 likely in an attempt to maintain chromosome stability. Despite the shift in cohesin distribution, 33 sister chromatid cohesion was partially attenuated in old cells and the frequency of chromosome 34 loss was increased. This age-induced CIN was exacerbated in strains lacking Sir2 and its paralog, 35Hst1, but suppressed in strains that stabilize the rDNA array due to the deletion of FOB1 or 36 through caloric restriction (CR). Furthermore, ectopic expression of MCD1 from a doxycycline-37 inducible promoter was sufficient to suppress to rDNA instability in aged cells and to extend 38 RLS. Taken together we conclude that age-induced depletion of cohesin and multiple other 39 nucleolar chromatin factors destabilize the rDNA locus, which then results in general CIN and 40 aneuploidy that shortens RLS. 41

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Section: Nuclear Protein Depletion During Replicative Aging As a Paramentioning

confidence: 90%

“…proportion of homologous recombination proteins were depleted in an independent analysis of 550 aged cells, with Rad52 the only one tested that was not affected (PAL et al 2018). These results 551 suggest there is at least some selectivity to the depletion of nuclear proteins in aged cells.…”

Section: Nuclear Protein Depletion During Replicative Aging As a Paramentioning

confidence: 99%

Depletion of limiting rDNA structural complexes triggers chromosomal instability and replicative aging ofSaccharomyces cerevisiae

Fine

Maqani

et al. 2018

Preprint

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“…Thus, the average pattern of epigenetic marks in a given cell line well correlates with the pattern of genes which are transcriptionally active or inactive within that cell line [1][2][3]. Dissecting the biophysical mechanisms leading to the de novo establishment, spreading and maintainance of epigenetic marks is consequently a key step towards a better understanding of the dynamic organisation of genomes and of chromosomal re-arrangement throughout the cell cycle [4], in cellular ageing [5] and pluripotency [6]. Notwithstanding their pivotal role, these mechanisms are still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

“…For this reason, simple models where epigenetic marks are stably deposited along chromatin [7, 9-11, 24, 25] are only crude approximations of a much more complex and dynamic scenario. Crucially, these "static" models fail to address key questions such as, how epigenetic patterns are first established along chromosomes, and how these change, for instance, with cellular ageing [5] or during disruptive events in the cell cycle [20]. In addition, an understanding of cell-to-cell variability in genome organisation [26,27] and of efficiency of the induced-pluripotency pathway [28] may be achieved only through models which can take into account the plasticity of the epigenetic landscape.…”

Section: Introductionmentioning

confidence: 99%

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Epigenetic Transitions and Knotted Solitons in Stretched Chromatin

Michieletto

Orlandini

Marenduzzo

2017

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The spreading and regulation of epigenetic marks on chromosomes is crucial to establish and maintain cellular identity. Nonetheless, the dynamical mechanism leading to the establishment and maintenance of a given, cell-line specific, epigenetic pattern is still poorly understood. In this work we propose, and investigate in silico, a possible experimental strategy to illuminate the interplay between 3D chromatin structure and epigenetic dynamics. We consider a set-up where a reconstituted chromatin fibre is stretched at its two ends (e.g., by laser tweezers), while epigenetic enzymes (writers) and chromatin-binding proteins (readers) are flooded into the system. We show that, by tuning the stretching force and the binding affinity of the readers for chromatin, the fibre undergoes a sharp transition between a stretched, epigenetically disordered, state and a crumpled, epigenetically coherent, one. We further investigate the case in which a knot is tied along the chromatin fibre, and find that the knotted segment enhances local epigenetic order, giving rise to "epigenetic solitons" which travel and diffuse along chromatin. Our results point to an intriguing coupling between 3D chromatin topology and epigenetic dynamics, which may be investigated via single molecule experiments.

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Rapid and extensive karyotype diversification in haploid clinical Candida auris isolates

et al. 2019

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Candida auris is a newly emerged pathogenic microbe, having been identified as a medically relevant fungus as recently as 2009. It is one of the most drug-resistant yeast species known to date and its emergence and population structure are unusual. Because of its recent emergence, we are largely ignorant about fundamental aspects of its general biology, life cycle, and population dynamics. Here, we report the karyotype variability of 26 C. auris strains representing the four main clades. We demonstrate that all strains are haploid and have a highly plastic karyotype containing five to seven chromosomes, which can undergo marked alterations within a short time frame when the fungus is put under genotoxic, heat, or osmotic stress. No simple correlation was found between karyotype pattern, drug resistance, and clade affiliation indicating that karyotype heterogeneity is rapidly evolving. As with other Candida species, these marked karyotype differences between isolates are likely to have an important impact on pathogenic traits of C. auris.Electronic supplementary materialThe online version of this article (10.1007/s00294-019-00976-w) contains supplementary material, which is available to authorized users.

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Impaired cohesion and homologous recombination during replicative aging in budding yeast

Abstract: How does the genome become unstable during aging?

Cited by 43 publications

References 55 publications

Depletion of limiting rDNA structural complexes triggers chromosomal instability and replicative aging ofSaccharomyces cerevisiae

Depletion of limiting rDNA structural complexes triggers chromosomal instability and replicative aging ofSaccharomyces cerevisiae

Epigenetic Transitions and Knotted Solitons in Stretched Chromatin

Rapid and extensive karyotype diversification in haploid clinical Candida auris isolates

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