Amoeba proteus and ploidy cycles: from simple model to complex issues

Berdieva, Mariia; Demin, S. Yu.; Goodkov, Andrew

doi:10.21685/1680-0826-2019-13-3-6

Cited by 8 publications

(10 citation statements)

References 16 publications

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“…IM coupling to telomere maintenance by ALT (or even substituting it) could resolve the long-standing puzzle of the Muller's Ratchet [95] in the obligately agamic amoeba existing on Earth for eons. They undergo cyclic polyploidy accompanied by chromatin diminution and express the orthologs of genes employed in meiosis of sexual eukaryotes Spo11, Mre11, Rad50, Rad51, Rad52, Mnd1, Dmc1, Msh, and Mlh [83,87,[96][97][98][99]. Archetti [100] recently presented calculations showing that asexual reproduction can replace sexual reproduction with inverted meiosis due to recombinative gene conversion, providing protection from the deleterious loss of heterozygosity and outweighing the cost of sex.…”

Section: Discussionmentioning

confidence: 99%

“Mitotic Slippage” and Extranuclear DNA in Cancer Chemoresistance: A Focus on Telomeres

Salmiņa

Bojko

Inashkina

et al. 2020

IJMS

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Mitotic slippage (MS), the incomplete mitosis that results in a doubled genome in interphase, is a typical response of TP53-mutant tumors resistant to genotoxic therapy. These polyploidized cells display premature senescence and sort the damaged DNA into the cytoplasm. In this study, we explored MS in the MDA-MB-231 cell line treated with doxorubicin (DOX). We found selective release into the cytoplasm of telomere fragments enriched in telomerase reverse transcriptase (hTERT), telomere capping protein TRF2, and DNA double-strand breaks marked by γH2AX, in association with ubiquitin-binding protein SQSTM1/p62. This occurs along with the alternative lengthening of telomeres (ALT) and DNA repair by homologous recombination (HR) in the nuclear promyelocytic leukemia (PML) bodies. The cells in repeated MS cycles activate meiotic genes and display holocentric chromosomes characteristic for inverted meiosis (IM). These giant cells acquire an amoeboid phenotype and finally bud the depolyploidized progeny, restarting the mitotic cycling. We suggest the reversible conversion of the telomerase-driven telomere maintenance into ALT coupled with IM at the sub-telomere breakage sites introduced by meiotic nuclease SPO11. All three MS mechanisms converging at telomeres recapitulate the amoeba-like agamic life-cycle, decreasing the mutagenic load and enabling the recovery of recombined, reduced progeny for return into the mitotic cycle.

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Section: Discussionmentioning

confidence: 99%

“Mitotic Slippage” and Extranuclear DNA in Cancer Chemoresistance: A Focus on Telomeres

Salmiņa

Bojko

Inashkina

et al. 2020

IJMS

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“…In turn, the early embryonal development in mammals also bears the phylogenetic features of the transition from unicellular to multicellular organisms. This transition evolved little new genes and it was mostly operating with multi-nuclearity, transient colonial forms, ploidy cycles [145,146], chromatin diminution [147], facultative sex [148], and asexual reproduction [149,150]. Interestingly, the earliest tumours were discovered within the same evolutionary forms, in basic metazoan Hydra, the authors concluded: "cancer is as old as multicellular life on Earth" [151].…”

Section: Cancer Cells Recapitulate the Stress-adaptive Programs Of Unmentioning

confidence: 99%

Resolution of Complex Issues in Genome Regulation and Cancer Requires Non-Linear and Network-Based Thermodynamics

Ērenpreisa

Giuliani

2019

IJMS

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The apparent lack of success in curing cancer that was evidenced in the last four decades of molecular medicine indicates the need for a global re-thinking both its nature and the biological approaches that we are taking in its solution. The reductionist, one gene/one protein method that has served us well until now, and that still dominates in biomedicine, requires complementation with a more systemic/holistic approach, to address the huge problem of cross-talk between more than 20,000 protein-coding genes, about 100,000 protein types, and the multiple layers of biological organization. In this perspective, the relationship between the chromatin network organization and gene expression regulation plays a fundamental role. The elucidation of such a relationship requires a non-linear thermodynamics approach to these biological systems. This change of perspective is a necessary step for developing successful 'tumour-reversion' therapeutic strategies.

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“…DNA content as well as nucleoli, heterochromatin and gonosomal chromatin bodies distributed into "subnuclei" according to their ploidy levels [3,[27][28][29][30]. By now, it is possible to consider it as variant of so called "polyploidy cycle" [31][32][33] that implies alternation of diploid and polyploid state in a cell lineage. It should be noted that such a phenomenon is fairly rare encountered in the cell lifespan and may be found in the "ancient" organisms like Protists [31][32][33] and some Invertebrates [34].…”

Section: Poly-and Aneuploidy Their Origin and Significancementioning

confidence: 99%

Genome Modifications Involved in Developmental Programs of the Placental Trophoblast

Zybina¹

2021

Cytogenetics - Classical and Molecular Strategies for Analysing Heredity Material

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The placental trophoblast cells give an example of profound genome modifications that lead to whole-genome multiplication, aneuploidy, under-replication of some genes or their clusters as well as, by contrast, gene amplification. These events are included into program of differentiation of functionally different cell lineages. In some cases the trophoblast cell differentiation involves depolyploidization achieved by non-mitotic division. Aneuploidy may be also accounted for by the unusual mitoses characteristic of Invertebrates and plants; in mammalian it may result from hypomethylation of centromere chromosome regions. The giant (endopolyploid) trophoblast cells organization includes “loose nucleosomes” accounted for by the non-canonical histone variants, i.e. H2AX, H2AZ, and H3. 3 . In the human extravillous trophoblast cells that, like murine TGC, invade endometrium, there occured significant changes of methylation as compared to non-invasive trophoblast cell populations . Meantime, some genes show hypermethylation connected with start of trophoblast lineages specification. Thus, despite the limited possibilities of chromosome visualization trophoblast cells represent an interesting model to investigate the role of modification of gene copy number and their expression that is important for the normal or abnormal cell differentiation.

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Amoeba proteus and ploidy cycles: from simple model to complex issues

Cited by 8 publications

References 16 publications

“Mitotic Slippage” and Extranuclear DNA in Cancer Chemoresistance: A Focus on Telomeres

“Mitotic Slippage” and Extranuclear DNA in Cancer Chemoresistance: A Focus on Telomeres

Resolution of Complex Issues in Genome Regulation and Cancer Requires Non-Linear and Network-Based Thermodynamics

Genome Modifications Involved in Developmental Programs of the Placental Trophoblast

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