The decreased exclusion of nuclear eccDNA: From molecular and subcellular levels to human aging and age-related diseases

Qiu, Guo-Hua; Zheng, Xintian; Fu, Mingjun; Huang, Cuiqin; Yang, Xiaoyan

doi:10.1016/j.arr.2021.101306

Cited by 27 publications

(16 citation statements)

References 110 publications

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“…In both human tumor cell lines and yeast, the significant correlation between the appearance of eccDNAs and the selective growth and/or resistance advantage of cells indicates that eccD-NAs influence the phenotype of cells. In yeast, eccDNAs participate in gene amplification [57] and thereby facilitate adaptation to nutrient-limiting environments [42,58,59], specific amino acid limitation [60], aging [10][11][12], and senescence caused by rDNA circles [61]. Similarly, in plants, eccDNA plays a role in transmissible herbicide resistance [54], and 49 of the 59 genes encoded by the eccDNA replicon are transcriptionally active when replicon-containing glyphosate-resistant plants are exposed to glyphosate [62].…”

Section: Function and Mechanism Of Eccdnamentioning

confidence: 99%

“…EccDNAs are sufficiently long to harbor their own origins of replication, are able to encode amino acids, and have been observed in tumor tissues, where they most frequently harbor oncogenes or genes related to drug resistance in cancer therapy [6][7][8][9]. Other functions of eccDNAs, such as functions in aging [10][11][12] and heterogeneity [13], as well as putative roles, including dosage compensation, have gradually been discovered. The genotype diversity and genomic plasticity within cancer cells are known to be affected by genome instability and genome alterations [14].…”

Section: Introductionmentioning

confidence: 99%

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Small extrachromosomal circular DNA (eccDNA): major functions in evolution and cancer

et al. 2021

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Extrachromosomal circular DNA (eccDNA) refers to a type of circular DNA that originate from but are likely independent of chromosomes. Due to technological advancements, eccDNAs have recently emerged as multifunctional molecules with numerous characteristics. The unique topological structure and genetic characteristics of eccDNAs shed new light on the monitoring, early diagnosis, treatment, and prediction of cancer. EccDNAs are commonly observed in both normal and cancer cells and function via different mechanisms in the stress response to exogenous and endogenous stimuli, aging, and carcinogenesis and in drug resistance during cancer treatment. The structural diversity of eccDNAs contributes to the function and numerical diversity of eccDNAs and thereby endows eccDNAs with powerful roles in evolution and in cancer initiation and progression by driving genetic plasticity and heterogeneity from extrachromosomal sites, which has been an ignored function in evolution in recent decades. EccDNAs show great potential in cancer, and we summarize the features, biogenesis, evaluated functions, functional mechanisms, related methods, and clinical utility of eccDNAs with a focus on their role in evolution and cancer.

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Section: Function and Mechanism Of Eccdnamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Small extrachromosomal circular DNA (eccDNA): major functions in evolution and cancer

et al. 2021

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“…EccDNAs are known for their broad existence across different species. There are increasing evidence showing that they play important functions in diverse biological processes, such as DNA damage repair ( Dillon et al, 2015 ), hypertranscription ( Dillon et al, 2015 ; Hull et al, 2019 ), homologous recombination ( Gresham et al, 2010 ), replication stress ( Dillon et al, 2015 ), gene amplification in cancer ( Paulsen et al, 2018 ; Morton et al, 2019 ), and ageing ( Zhu et al, 2017 ; Hull et al, 2019 ; Qiu et al, 2021 ). Recently, Zhang’s research team from Boston reported that eccDNA was potent innate immunostimulants ( Wang et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Characterization of Plasma Extrachromosomal Circular DNA in Gouty Arthritis

Pang

Pan²,

Li³

et al. 2022

Front. Genet.

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Objective: Extrachromosomal circular DNA elements (eccDNAs) are known for their broad existence in cells and plasma, which may potentially play important roles in many biological processes. Our aim was to identify potentially functional or marked eccDNAs in gout patients.Methods: The Circle-Seq approach was applied for eccDNA detection from plasma in acute gout patients and healthy controls. Further analysis was performed on the distribution of genomic elements and eccDNA gene annotations in two groups.Results: We detected 57,216 and 109,683 eccDNAs from the acute gout and healthy control plasma, respectively. EccDNAs were mapped to the reference genome to identify diverse classes of genomic elements and there was no significant difference of eccDNAs on genomic element annotation between gout and control group. A total of 256 eccDNA-associated genes were detected as gout unique eccDNA genes, including COL1A1 and EPB42, which potentially contribute to hyperuricemia and gout, and a couple of genes involved in inflammation or immune response. Enrichment analysis showed that these eccDNA genes were highly correlated with defense response, stress response, and immune and inflammatory responses, including T cell receptor signaling pathway, Fc epsilon RI signaling pathway, and JAK-STAT signaling pathway.Conclusion: Our discovery reveals the novel potential biological roles of plasma eccDNAs in gouty arthritis.

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“…Extrachromosomal circular DNAs from chromosomal origin are common in yeast and human cells (Møller et al , 2015, 2018; Qiu et al , 2021). However, how they are produced and whether they interfere with DNA metabolism or DNA damage repair remain elusive.…”

Section: Discussionmentioning

confidence: 99%

Telomeric C‐circles localize at nuclear pore complexes in Saccharomyces cerevisiae

et al. 2022

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As in human cells, yeast telomeres can be maintained in cells lacking telomerase activity by recombination‐based mechanisms known as ALT (Alternative Lengthening of Telomeres). A hallmark of ALT human cancer cells are extrachromosomal telomeric DNA elements called C‐circles, whose origin and function have remained unclear. Here, we show that extrachromosomal telomeric C‐circles in yeast can be detected shortly after senescence crisis and concomitantly with the production of survivors arising from “type II” recombination events. We uncover that C‐circles bind to the nuclear pore complex (NPC) and to the SAGA‐TREX2 complex, similar to other non‐centromeric episomal DNA. Disrupting the integrity of the SAGA/TREX2 complex affects both C‐circle binding to NPCs and type II telomere recombination, suggesting that NPC tethering of C‐circles facilitates formation and/or propagation of the long telomere repeats characteristic of type II survivors. Furthermore, we find that disruption of the nuclear diffusion barrier impairs type II recombination. These results support a model in which concentration of C‐circles at NPCs benefits type II telomere recombination, highlighting the importance of spatial coordination in ALT‐type mechanisms of telomere maintenance.

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The decreased exclusion of nuclear eccDNA: From molecular and subcellular levels to human aging and age-related diseases

Cited by 27 publications

References 110 publications

Small extrachromosomal circular DNA (eccDNA): major functions in evolution and cancer

Small extrachromosomal circular DNA (eccDNA): major functions in evolution and cancer

Characterization of Plasma Extrachromosomal Circular DNA in Gouty Arthritis

Telomeric C‐circles localize at nuclear pore complexes in Saccharomyces cerevisiae

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