DNA strand methylation and sister chromatid exchanges in mammalian cells in vitro

Albanesi, Tiziana; Polani, Stefania; Cozzi, Renata; Perticone, Paolo

doi:10.1016/s0027-5107(99)00112-8

Cited by 14 publications

(4 citation statements)

References 33 publications

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“…In addition, hemimethylation might stimulate inter-sister chromatid recombination. This idea is supported by early studies in cultured mammalian somatic cells that implicated DNA hemimethylation in increased sister chromatid exchanges in mitosis [ 60 , 61 ]. In addition, given the essential role of the mismatch repair pathway in meiosis, it is tempting to speculate that DNA hemimethylation may influence the usage of sister chromatids in MPI akin to methylation-directed mismatch repair system of E. coli [ 62 ].…”

Section: Discussionmentioning

confidence: 85%

Transient reduction of DNA methylation at the onset of meiosis in male mice

Gaysinskaya

Miller

Luca

et al. 2018

Epigenetics & Chromatin

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BackgroundMeiosis is a specialized germ cell cycle that generates haploid gametes. In the initial stage of meiosis, meiotic prophase I (MPI), homologous chromosomes pair and recombine. Extensive changes in chromatin in MPI raise an important question concerning the contribution of epigenetic mechanisms such as DNA methylation to meiosis. Interestingly, previous studies concluded that in male mice, genome-wide DNA methylation patters are set in place prior to meiosis and remain constant subsequently. However, no prior studies examined DNA methylation during MPI in a systematic manner necessitating its further investigation.ResultsIn this study, we used genome-wide bisulfite sequencing to determine DNA methylation of adult mouse spermatocytes at all MPI substages, spermatogonia and haploid sperm. This analysis uncovered transient reduction of DNA methylation (TRDM) of spermatocyte genomes. The genome-wide scope of TRDM, its onset in the meiotic S phase and presence of hemimethylated DNA in MPI are all consistent with a DNA replication-dependent DNA demethylation. Following DNA replication, spermatocytes regain DNA methylation gradually but unevenly, suggesting that key MPI events occur in the context of hemimethylated genome. TRDM also uncovers the prior deficit of DNA methylation of LINE-1 retrotransposons in spermatogonia resulting in their full demethylation during TRDM and likely contributing to the observed mRNA and protein expression of some LINE-1 elements in early MPI.ConclusionsOur results suggest that contrary to the prevailing view, chromosomes exhibit dynamic changes in DNA methylation in MPI. We propose that TRDM facilitates meiotic prophase processes and gamete quality control.Electronic supplementary materialThe online version of this article (10.1186/s13072-018-0186-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 85%

Transient reduction of DNA methylation at the onset of meiosis in male mice

Gaysinskaya

Miller

Luca

et al. 2018

Epigenetics & Chromatin

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“…Each of these approaches causes global and non-specific changes in DNA methylation. This fact appears to raise troubling issues for clinical strategies utilizing these drugs, in that DNA hypomethylation has been linked to genomic instability, elevated rates of mutation, and the activation of retrotransposable elements (Albanesi et al, 1999;Chen et al, 1998;Neidhart et al, 2000). Additionally, 5-aza-CdR itself may act as a mutagen as the result of interactions between 5-aza-cytosine and DNMT1 (Jackson-Grusby et al, 1997).…”

Section: Evaluating the Efficacy And Toxicity Of Gene Reactivation Stmentioning

confidence: 99%

Reactivating the expression of methylation silenced genes in human cancer

2002

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“…5-azacytidine, ethionine, and 9-b-D-arabinofuranosyl-adenine-induced hypomethylation increases sister chromatid exchange (SCE) formation in mammalian cells [ 43 ]. SCEs occur only after a second cell cycle following the demethylating pulse, indicating that the key event comprises demethylation of the old parental DNA strand.…”

Section: Dna Methylation and Induction Of Chromosomal Instabilitymentioning

confidence: 99%

The Epigenetic Origin of Aneuploidy

Herrera¹,

Prada²,

Andonegui³

et al. 2008

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Theodore Boveri, eminent German pathologist, observed aneuploidy in cancer cells more than a century ago and suggested that cancer cells derived from a single progenitor cell that acquires the potential for uncontrolled continuous proliferation. Currently, it is well known that aneuploidy is observed in virtually all cancers. Gain and loss of chromosomal material in neoplastic cells is considered to be a process of diversification that leads to survival of the fittest clones. According to Darwin's theory of evolution, the environment determines the grounds upon which selection takes place and the genetic characteristics necessary for better adaptation. This concept can be applied to the carcinogenesis process, connecting the ability of cancer cells to adapt to different environments and to resist chemotherapy, genomic instability being the driving force of tumor development and progression. What causes this genome instability? Mutations have been recognized for a long time as the major source of genome instability in cancer cells. Nevertheless, an alternative hypothesis suggests that aneuploidy is a primary cause of genome instability rather than solely a simple consequence of the malignant transformation process. Whether genome instability results from mutations or from aneuploidy is not a matter of discussion in this review. It is most likely both phenomena are intimately related; however, we will focus on the mechanisms involved in aneuploidy formation and more specifically on the epigenetic origin of aneuploid cells. Epigenetic inheritance is defined as cellular information-other than the DNA sequence itself-that is heritable during cell division. DNA methylation and histone modifications comprise two of the main epigenetic modifications that are important for many physiological and pathological conditions, including cancer. Aberrant DNA methylation is the most common molecular cancer-cell lesion, even more frequent than gene mutations; tumor suppressor gene silencing by CpG island promoter hypermethylation is perhaps the most frequent epigenetic modification in cancer cells. Epigenetic characteristics of cells may be modified by several factors including environmental exposure, certain nutrient deficiencies, radiation, etc. Some of these alterations have been correlated with the formation of aneuploid cells in vivo. A growing body of evidence suggests that aneuploidy is produced and caused by chromosomal instability. We propose and support in this manuscript that not only genetics but also epigenetics, contribute in a major fashion to aneuploid cell formation.

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DNA strand methylation and sister chromatid exchanges in mammalian cells in vitro

Cited by 14 publications

References 33 publications

Transient reduction of DNA methylation at the onset of meiosis in male mice

Transient reduction of DNA methylation at the onset of meiosis in male mice

Reactivating the expression of methylation silenced genes in human cancer

The Epigenetic Origin of Aneuploidy

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