Folate deficiency facilitates recruitment of upstream binding factor to hot spots of DNA double-strand breaks of rRNA genes and promotes its transcription

Xie, Qijun; Li, Caihua; Song, Xiaozhen; Wu, Lihua; Jiang, Qian; Qiu, Zhiyong; Cao, Haiyan; Yu, Kaihui; Wan, Chunlei; Li, Jianting; Yang, Feng; Huang, Zebing; Niu, Bo; Jiang, Zhengwen; Zhang, Ting

doi:10.1093/nar/gkw1208

Cited by 23 publications

(23 citation statements)

References 73 publications

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“…; Xie et al . ). Indeed, increased occurrence of DSBs, mitotic deficits and apoptosis were observed in fibroblasts from patients with the E210K mutation (Toro et al .…”

Section: Neurodevelopmental Consequences Of Genetic Defects Of Ribosomentioning

confidence: 97%

“…A recent report that used an unbiased approach to determine hot spots for DNA double‐strand breaks in folate‐deficient mouse embryonic stem cells identified the intergenic spacer region of rDNA as being particularly sensitive to damage (Xie et al . ). That damage was associated with altered epigenetic landscape of rDNA, increased recruitment of UBTF1 and higher expression of rRNA.…”

Section: Neuroteratogenic Factors That Target Ribosomal Biogenesismentioning

confidence: 97%

“…The latter effect was also found in samples from human fetuses with NTD (Xie et al . ). Thus, RS‐mediated impairment of neuroepithelium proliferation or RS‐induced apoptosis could contribute to NTD.…”

Section: Neuroteratogenic Factors That Target Ribosomal Biogenesismentioning

confidence: 97%

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Ribosomal biogenesis as an emerging target of neurodevelopmental pathologies

Hetman

Słomnicki

2018

Journal of Neurochemistry

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Development of the nervous system is carried out by complex gene expression programs that are regulated at both transcriptional and translational level. In addition, quality control mechanisms such as the TP53-mediated apoptosis or neuronal activity-stimulated survival ensure successful neurogenesis and formation of functional circuitries. In the nucleolus, production of ribosomes is essential for protein synthesis. In addition, it participates in chromatin organization and regulates the TP53 pathway via the ribosomal stress response. Its tight regulation is required for maintenance of genomic integrity. Mutations in several ribosomal components and trans-acting ribosomal biogenesis factors result in neurodevelopmental syndromes that present with microcephaly, autism, intellectual deficits and/or progressive neurodegeneration. Furthermore, ribosomal biogenesis is perturbed by exogenous factors that disrupt neurodevelopment including alcohol or Zika virus. In this review, we present recent literature that argues for a role of dysregulated ribosomal biogenesis in pathogenesis of various neurodevelopmental syndromes. We also discuss potential mechanisms through which such dysregulation may lead to cellular pathologies of the developing nervous system including insufficient proliferation and/or loss of neuroprogenitors cells, apoptosis of immature neurons, altered neuronal morphogenesis, and neurodegeneration.

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“…; Xie et al . ). Indeed, increased occurrence of DSBs, mitotic deficits and apoptosis were observed in fibroblasts from patients with the E210K mutation (Toro et al .…”

Section: Neurodevelopmental Consequences Of Genetic Defects Of Ribosomentioning

confidence: 97%

Section: Neuroteratogenic Factors That Target Ribosomal Biogenesismentioning

confidence: 97%

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Ribosomal biogenesis as an emerging target of neurodevelopmental pathologies

Hetman

Słomnicki

2018

Journal of Neurochemistry

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“…Epigenetic status of the rDNA impacts the susceptibility of rDNA to breakage upon RS caused by folate deficiency, an essential factor for nucleotide biosynthesis. Folate deficiency enhanced DNA damage in the whole-genome [ 85 ], but it was particularly prominent in several specific regions of IGSs within rDNA clusters [ 86 ]. These breaks sites correspond to histone H3K4me1 mark sites and positively correlate with increased recruitment of UBF to rDNA genes and their enhanced transcription [ 86 ].…”

Section: Conflicts Between Replication and Transcription Machineries mentioning

confidence: 99%

Nucleolus as an emerging hub in maintenance of genome stability and cancer pathogenesis

et al. 2018

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The nucleolus is the major site for synthesis of ribosomes, complex molecular machines that are responsible for protein synthesis. A wealth of research over the past 20 years has clearly indicated that both quantitative and qualitative alterations in ribosome biogenesis can drive the malignant phenotype via dysregulation of protein synthesis. However, numerous recent proteomic, genomic, and functional studies have implicated the nucleolus in the regulation of processes that are unrelated to ribosome biogenesis, including DNA-damage response, maintenance of genome stability and its spatial organization, epigenetic regulation, cell-cycle control, stress responses, senescence, global gene expression, as well as assembly or maturation of various ribonucleoprotein particles. In this review, the focus will be on features of rDNA genes, which make them highly vulnerable to DNA damage and intra- and interchromosomal recombination as well as built-in mechanisms that prevent and repair rDNA damage, and how dysregulation of this interplay affects genome-wide DNA stability, gene expression and the balance between euchromatin and heterochromatin. We will also present the most recent insights into how malfunction of these cellular processes may be a central driving force of human malignancies, and propose a promising new therapeutic approach for the treatment of cancer.

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“…MTX also produces double strands breaks in the DNA of rRNA genes in mouse ESC that were similar to the reported hot spots of double stranded breaks in human rRNA genes in H1‐hESCs. Finally, MTX treatment has been shown to produce DNA breakage sites of rRNA gene units corresponding almost exclusively to histone H3K4me1 marks (Xie et al, ).…”

Section: Chemical Agentsmentioning

confidence: 99%

The role of teratogens in neural crest development

Cerrizuela

Vega-Lopez

Aybar

2020

Birth Defects Research

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The neural crest (NC), discovered by Wilhelm His 150 years ago, gives rise to a multipotent migratory embryonic cell population that generates a remarkably diverse and important array of cell types during the development of the vertebrate embryo. These cells originate in the neural plate border (NPB), which is the ectoderm between the neural plate and the epidermis. They give rise to the neurons and glia of the peripheral nervous system, melanocytes, chondrocytes, smooth muscle cells, odontoblasts and neuroendocrine cells, among others. Neurocristopathies are a class of congenital diseases resulting from the abnormal induction, specification, migration, differentiation or death of NC cells (NCCs) during embryonic development and have an important medical and societal impact. In general, congenital defects affect an appreciable percentage of newborns worldwide. Some of these defects are caused by teratogens, which are agents that negatively impact the formation of tissues and organs during development. In this review, we will discuss the teratogens linked to the development of many birth defects, with a strong focus on those that specifically affect the development of the NC, thereby producing neurocristopathies.Although increasing attention is being paid to the effect of teratogens on embryonic development in general, there is a strong need to critically evaluate the specific role of these agents in NC development. Therefore, increased understanding of the role of these factors in NC development will contribute to the planning of strategies aimed at the prevention and treatment of human neurocristopathies, whose etiology was previously not considered.

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Folate deficiency facilitates recruitment of upstream binding factor to hot spots of DNA double-strand breaks of rRNA genes and promotes its transcription

Cited by 23 publications

References 73 publications

Ribosomal biogenesis as an emerging target of neurodevelopmental pathologies

Ribosomal biogenesis as an emerging target of neurodevelopmental pathologies

Nucleolus as an emerging hub in maintenance of genome stability and cancer pathogenesis

The role of teratogens in neural crest development

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