Chromosome Instability through the Ages: Parallels between Speciation and Somatic (Cancer) Evolution

Macdonald, Catriona M. M.; McClelland, Sarah E.

doi:10.1016/j.tig.2021.05.003

Cited by 3 publications

(4 citation statements)

References 14 publications

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“…An increase in the division number of small cells (e.g. stem cells) may simply translate into higher cancer incidence due to errors in DNA copying with each single cell multiplication [ 10 , 16 , 27 , 46 , 47 ]. Second, the size of cells is one of the determinants of the cellular metabolic rate and costs of maintenance of the membrane gradients [ 42 ].…”

Section: Cell Size Variation and Its Implication For Carcinogenesismentioning

confidence: 99%

“…Such systems should emulate mechanisms of natural selection and thus markedly depart from the research paradigm of simplified animal models having knocked-out or overexpressed genes widely adopted in oncology and bearing unclear relations to the evolutionary context of carcinogenesis. Although single gene manipulation has greatly contributed to considerable progress in the field of genetics and cell biology, a deeper understanding of tumor initiation and its progression requires an evolutionary approach [ 36 , 47 , 56 ]. Genetically manipulated models disregard combinations of allelic variants and interactions between multiple loci, which significantly affect anticancer mechanisms molded by natural selection [ 36 ].…”

Section: Cell Size Variation and Its Implication For Carcinogenesismentioning

confidence: 99%

“… 4 , 5 , 10 ], potential differences in cancer propensity arise due to mutations in the key genes affecting their expression. Genes dysfunction may be additionally enhance by chromosomal instability (changes in chromosomal number and/or its structure) usually result from erroneous DNA replication or repair [ 47 ]. However today, remaining challenge in any cancer studies is to determine the main drivers responsible for organism malignancy, which concomitantly stand as a promising targets for a future therapeutic action [ 64 ].…”

Section: Cell Size Variation and Its Implication For Carcinogenesismentioning

confidence: 99%

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Cell size, body size and Peto’s paradox

Maciak

2022

BMC Ecol Evo

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Carcinogenesis is one of the leading health concerns afflicting presumably every single animal species, including humans. Currently, cancer research expands considerably beyond medicine, becoming a focus in other branches of natural science. Accumulating evidence suggests that a proportional scale of tumor deaths involves domestic and wild animals and poses economical or conservation threats to many species. Therefore, understanding the genetic and physiological mechanisms of cancer initiation and its progression is essential for our future action and contingent prevention. From this perspective, I used an evolutionary-based approach to re-evaluate the baseline for debate around Peto’s paradox. First, I review the background of information on which current understanding of Peto’s paradox and evolutionary concept of carcinogenesis have been founded. The weak points and limitations of theoretical modeling or indirect reasoning in studies based on intraspecific, comparative studies of carcinogenesis are highlighted. This is then followed by detail discussion of an effect of the body mass in cancer research and the importance of cell size in consideration of body architecture; also, I note to the ambiguity around cell size invariance hypothesis and hard data for variability of cell size across species are provided. Finally, I point to the new research area that is driving concepts to identify exact molecular mechanisms promoting the process of tumorigenesis, which in turn may provide a proximate explanation of Peto’s paradox. The novelty of the approach proposed therein lies in intraspecies testing of the effect of differentiation of cell size/number on the probability of carcinogenesis while controlling for the confounding effect of body mass/size.

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Section: Cell Size Variation and Its Implication For Carcinogenesismentioning

confidence: 99%

Section: Cell Size Variation and Its Implication For Carcinogenesismentioning

confidence: 99%

Section: Cell Size Variation and Its Implication For Carcinogenesismentioning

confidence: 99%

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Cell size, body size and Peto’s paradox

Maciak

2022

BMC Ecol Evo

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“…Genetic diseases and evolution can be driven by large scale structural changes to chromosomes, including chromosomal translocations [1][2][3]. Translin is a conserved nucleic acid binding protein first identified in humans by its ability to bind to malignant disease-associated chromosomal translocation breakpoint junctions, which resulted in the postulate that it mediates genetic recombination [4].…”

Section: Introductionmentioning

confidence: 99%

Translin facilitates RNA polymerase II dissociation and suppresses genome instability during RNase H2- and Dicer-deficiency

et al. 2022

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The conserved nucleic acid binding protein Translin contributes to numerous facets of mammalian biology and genetic diseases. It was first identified as a binder of cancer-associated chromosomal translocation breakpoint junctions leading to the suggestion that it was involved in genetic recombination. With a paralogous partner protein, Trax, Translin has subsequently been found to form a hetero-octomeric RNase complex that drives some of its functions, including passenger strand removal in RNA interference (RNAi). The Translin-Trax complex also degrades the precursors to tumour suppressing microRNAs in cancers deficient for the RNase III Dicer. This oncogenic activity has resulted in the Translin-Trax complex being explored as a therapeutic target. Additionally, Translin and Trax have been implicated a wider range of biological functions ranging from sleep regulation to telomere transcript control. Here we reveal a Trax- and RNAi-independent function for Translin in dissociating RNA polymerase II from its genomic template, with loss of Translin function resulting in increased transcription-associated recombination and elevated genome instability. This provides genetic insight into the longstanding question of how Translin might influence chromosomal rearrangements in human genetic diseases and provides important functional understanding of an oncological therapeutic target.

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