Proliferation of Double-Strand Break-Resistant Polyploid Cells Requires  Drosophila  FANCD2

Bretscher, Heidi; Fox, Donald T.

doi:10.1016/j.devcel.2016.05.004

Cited by 40 publications

(91 citation statements)

References 68 publications

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“…This is possible because polyploid cells in tissues such as the salivary gland have intrinsically low levels of p53 protein and also suppress the expression of pro-apoptotic genes 22 . It has also been shown in various tissues and organisms that DNA damage can induce polyploidisation 43,54,55 . Since we observe a modest upregulation of p53 as well as a p53-dependent gene expression signature in older OLs, we asked if the induction of polyploidy in neurons is p53 dependent.…”

Section: Polyploidy Accumulation In Neurons Is P53-independentmentioning

confidence: 99%

Polyploidy in the adultDrosophilabrain

Nandakumar

Grushko

Buttitta

2019

Preprint

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Long-lived cells such as terminally differentiated postmitotic neurons and glia must cope with the accumulation of damage over the course of an animal's lifespan. How long-lived cells deal with ageing-related damage is poorly understood. Here we show that polyploid cells accumulate in the ageing adult fly brain and that polyploidy protects against DNA damage-induced cell death. Multiple types of neurons and glia that are diploid at eclosion, become polyploid with age in the adult Drosophila brain. The optic lobes exhibit the highest levels of polyploidy, associated with an elevated DNA damage response in this brain region with age. Inducing oxidative stress or exogenous DNA damage leads to an earlier onset of polyploidy, and polyploid cells in the adult brain are more resistant to DNA damage-induced cell death than diploid cells. Our results suggest polyploidy may serve a protective role for neurons and glia in ageing Drosophila melanogaster brains. for providing fly stocks, particularly the labs of Cheng-

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Section: Polyploidy Accumulation In Neurons Is P53-independentmentioning

confidence: 99%

Polyploidy in the adultDrosophilabrain

Nandakumar

Grushko

Buttitta

2019

Preprint

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“…This suggests a trade-off in which cells generate copy number variation and DNA breaks in exchange for a reduction in replication. Since Drosophila polyploid cells down-regulate the apoptotic machinery, the errors caused during replication can be survived by the cell (Mehrotra et al 2008; Zhang et al 2014; Bretscher and Fox 2016). Ciliates undergo an even more extreme genome rearrangement after the polytene stage; so, small amounts of underreplication may not be detrimental.…”

Section: Common Structural Features Of Polytene Chromosomesmentioning

confidence: 99%

Polyteny: still a giant player in chromosome research

Stormo

Fox

2017

Chromosome Res

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In this era of high-resolution mapping of chromosome territories, topological interactions, and chromatin states, it is increasingly appreciated that the positioning of chromosomes and their interactions within the nucleus is critical for cellular function. Due to their large size and distinctive structure, polytene chromosomes have contributed a wealth of knowledge regarding chromosome regulation. In this review, we discuss the diversity of polytene chromosomes in nature and in disease, examine the recurring structural features of polytene chromosomes in terms of what they reveal about chromosome biology, and discuss recent advances regarding how polytene chromosomes are assembled and disassembled. After over 130 years of study, these giant chromosomes are still powerful tools to understand chromosome biology.

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“…This was observed in brains expressing H2Av-RFP to visualize DNA and the kinetochore protein Spc25 (a component of the Ncd80 complex) [16]. Acentric chromosomes are characteristic of cells that experience genomic instability [17] and have been observed in Drosophila papillar cells [18]. In Ctrl cells we never observed mitotic chromosomes lacking Spc25 (n=16 NBs from 2 brains) ( Figure 1G).…”

Section: Polyploid Nbs Accumulate High Number Of Incomplete Chromosommentioning

confidence: 59%

Cell Cycle Asynchrony Generates DNA Damage at Mitotic Entry in Polyploid Cells

Nano

Simon

Pennetier

et al. 2019

Preprint

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Polyploidy arises from the gain of complete chromosomes sets [1] and is known to promote cancer genome evolution. Recent evidence suggests that a large proportion of human tumours experience whole genome duplications (WGDs), which might favour the generation of highly abnormal karyotypes within a short time frame, rather than in a stepwise manner [2][3][4][5][6].However, the molecular mechanisms linking whole genome duplication to genetic instability remain poorly understood. Further, possible mechanisms responsible for rapid genome reshuffling have not been described yet. Using repeated cytokinesis failure to induce polyploidization of Drosophila neural stem cells (NSCs, also called neuroblasts -NBs), we investigated the consequences of polyploidy in vivo. Here, we show that polyploid NSCs accumulate high levels of chromosome instability. Surprisingly, we found that DNA damage is generated in a subset of nuclei of polyploid NBs during mitosis, in an asymmetric manner.Importantly, our observations in flies were confirmed in mouse NSCs (mNSCs) after acute cytokinesis inhibition. Interestingly, DNA damage occurs in nuclei that were not ready to enter mitosis but were forced to do so when exposed to the mitotic environment of neighbouring nuclei within the same cell. Additionally, we found that polyploid cells are cell cycle asynchronous and forcing cell cycle synchronization is sufficient to lower the levels of DNA damage generated during mitosis. Overall, this work supports a model in which DNA damage at mitotic entry can generate a mutated genetic landscape that contributes to the onset of genetic instability.

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Proliferation of Double-Strand Break-Resistant Polyploid Cells Requires Drosophila FANCD2

Cited by 40 publications

References 68 publications

Polyploidy in the adultDrosophilabrain

Polyploidy in the adultDrosophilabrain

Polyteny: still a giant player in chromosome research

Cell Cycle Asynchrony Generates DNA Damage at Mitotic Entry in Polyploid Cells

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