Replication stress, a source of epigenetic aberrations in cancer?

Jasencakova, Zuzana; Groth, Anja

doi:10.1002/bies.201000055

Cited by 28 publications

(24 citation statements)

References 121 publications

(170 reference statements)

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“…They were both highly expressed in iPS cells but showed comparatively low expression in ES cells. This result is consistent with the former studies that showed that the reprogramming process is somewhat similar to tumor development (Halazonetis et al, 2008;Kawamura et al, 2009;Marión et al, 2009;Utikal et al, 2009;Edel et al, 2010;Jasencakova and Groth, 2010;Menendez et al, 2010;Gupta et al, 2011). LEFTY expression has been recognized as a stemness marker owing to its enrichment both in undifferentiated ES cells and in blastocysts.…”

Section: Discussionsupporting

confidence: 92%

Gene expression profiling of somatic and pluripotent cells reveals novel pathways involved in reprogramming

et al. 2015

Genet. Mol. Res.

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ABSTRACT. We investigated gene expression in embryonic stem (ES) cells, induced pluripotent stem (iPS) cells, and fibroblasts. Microarray expression data sets obtained from the Gene Expression Omnibus were analyzed using the Partek software. Human genes from ES cells, iPS cells, and fibroblasts were ranked from low to high according to their expression levels. The gene expression mode in iPS cells was much more like the mode in ES cells, and the expression levels of fibroblast genes fluctuated more dramatically than those of iPS and ES cells. The number of genes with significantly different expression was lower in the iPS and ES cells. Several genes with the expression levels that were significantly different between ES and iPS cells were found, including LEFTY2, DLK1, and NLRP2. Four genes belonged to the low expression category in fibroblasts with the high expression category occurring in ES cells, i.e., HESRG, PROM1, NTS, and LRRN1. Analyzing the expression of these genes is helpful to elucidate the mechanisms of cell fate regulation and efficiently obtain iPS cells.

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Section: Discussionsupporting

confidence: 92%

Gene expression profiling of somatic and pluripotent cells reveals novel pathways involved in reprogramming

et al. 2015

Genet. Mol. Res.

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“…Chromatin alterations can arise as a consequence of perturbed histone dynamics in response to replication stress, which may facilitate stochastic epigenetic silencing by laying down repressive histone marks at sites of fork stalling[54]. Our in-detailed study in the fission yeast S .…”

Section: Discussionmentioning

confidence: 99%

Replication stress affects the fidelity of nucleosome-mediated epigenetic inheritance

Li¹,

Yi²,

Agbu³

et al. 2017

PLoS Genet

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The fidelity of epigenetic inheritance or, the precision by which epigenetic information is passed along, is an essential parameter for measuring the effectiveness of the process. How the precision of the process is achieved or modulated, however, remains largely elusive. We have performed quantitative measurement of epigenetic fidelity, using position effect variegation (PEV) in Schizosaccharomyces pombe as readout, to explore whether replication perturbation affects nucleosome-mediated epigenetic inheritance. We show that replication stresses, due to either hydroxyurea treatment or various forms of genetic lesions of the replication machinery, reduce the inheritance accuracy of CENP-A/Cnp1 nucleosome positioning within centromere. Mechanistically, we demonstrate that excessive formation of single-stranded DNA, a common molecular abnormality under these conditions, might have correlation with the reduction in fidelity of centromeric chromatin duplication. Furthermore, we show that replication stress broadly changes chromatin structure at various loci in the genome, such as telomere heterochromatin expanding and mating type locus heterochromatin spreading out of the boundaries. Interestingly, the levels of inheritable expanding at sub-telomeric heterochromatin regions are highly variable among independent cell populations. Finally, we show that HU treatment of the multi-cellular organisms C. elegans and D. melanogaster affects epigenetically programmed development and PEV, illustrating the evolutionary conservation of the phenomenon. Replication stress, in addition to its demonstrated role in genetic instability, promotes variable epigenetic instability throughout the epigenome.

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“…In theory, any perturbation of DNA replication and especially of fork integrity could lead to aberrant reassembly of chromatin (66). However, such events do not necessarily lead to enhanced or reduced epigenetic stability.…”

Section: Discussionmentioning

confidence: 99%

Analysis of epigenetic stability and conversions in Saccharomyces cerevisiae reveals a novel role of CAF-I in position-effect variegation

Jeffery

Wyse

Rehman

et al. 2013

Nucleic Acids Research

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Position-effect variegation (PEV) phenotypes are characterized by the robust multigenerational repression of a gene located at a certain locus (often called gene silencing) and occasional conversions to fully active state. Consequently, the active state then persists with occasional conversions to the repressed state. These effects are mediated by the establishment and maintenance of heterochromatin or euchromatin structures, respectively. In this study, we have addressed an important but often neglected aspect of PEV: the frequency of conversions at such loci. We have developed a model and have projected various PEV scenarios based on various rates of conversions. We have also enhanced two existing assays for gene silencing in Saccharomyces cerevisiae to measure the rate of switches from repressed to active state and vice versa. We tested the validity of our methodology in Δsir1 cells and in several mutants with defects in gene silencing. The assays have revealed that the histone chaperone Chromatin Assembly Factor I is involved in the control of epigenetic conversions. Together, our model and assays provide a comprehensive methodology for further investigation of epigenetic stability and position effects.

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Replication stress, a source of epigenetic aberrations in cancer?

Cited by 28 publications

References 121 publications

Gene expression profiling of somatic and pluripotent cells reveals novel pathways involved in reprogramming

Gene expression profiling of somatic and pluripotent cells reveals novel pathways involved in reprogramming

Replication stress affects the fidelity of nucleosome-mediated epigenetic inheritance

Analysis of epigenetic stability and conversions in Saccharomyces cerevisiae reveals a novel role of CAF-I in position-effect variegation

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