Molecular structure and evolution mechanism of two populations of double minutes in human colorectal cancer cells

Jia, Xueyuan; Guan, Rongwei; Cui, Xiaobo; Zhu, Jing; Liu, Peng; Zhang, Ling; Wang, Dong; Zhang, Yang; Dong, Kai; Wu, Jie; Ji, Wei; Ji, Guohua; Bai, Jing; Yu, Jingcui; Ye, Yu; Sun, Wenjing; Zhang, Feng; Fu, Songbin

doi:10.1111/jcmm.16035

Cited by 11 publications

(9 citation statements)

References 45 publications

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“… [ 78 , 79 ] Colorectal cancer Not define NA Chromothripsis, a process of multistep evolution that drives eccDNA formation eccDNA may drive cancer progression. [ 80 ] Leukemia MYC Hydroxyurea NA Hydroxyurea inhibits tumorigenicity by eliminating amplified MYC on eccDNAs. [ 81 ] Leukemia c-Myc Hydroxyurea and retinoic acid NA Hydroxyurea inhibits tumorigenicity by eliminating c-Myc-bearing eccDNAs.…”

Section: Function and Mechanism Of Eccdnamentioning

confidence: 99%

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%

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

et al. 2021

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“…Researchers also identified two distinct ecDNA populations in the NCI‐H716 cell line, demonstrated their heterogeneity in cancer cells, and successfully constructed their molecular structure. The distribution of amplicons in the two different ecDNA populations suggests that the multi-step evolutionary model is more suitable for the ecDNA generating module of the NCI‐H716 cell line [ 120 ].…”

Section: The Role Of Eccdna In Cancermentioning

confidence: 99%

Extrachromosomal circular DNA: a new potential role in cancer progression

et al. 2021

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Extrachromosomal circular DNA (eccDNA) is considered a circular DNA molecule that exists widely in nature and is independent of conventional chromosomes. eccDNA can be divided into small polydispersed circular DNA (spcDNA), telomeric circles (t-circles), microDNA, and extrachromosomal DNA (ecDNA) according to its size and sequence. Multiple studies have shown that eccDNA is the product of genomic instability, has rich and important biological functions, and is involved in the occurrence of many diseases, including cancer. In this review, we focus on the discovery history, formation process, characteristics, and physiological functions of eccDNAs; the potential functions of various eccDNAs in human cancer; and the research methods employed to study eccDNA.

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“…The larger eccDNA (>10 kb), termed double minutes, have been well categorized and studied due to their contribution to cancer growth by sustaining and amplifying full gene sequences through circular molecules that contain promoters, enhancers and replication origin sequences. They are often composed of DNA segments from multiple loci (multilocular) and their massive size enables these molecules to be visible through fluorescent microscopy during normal karyotyping ( 9–11 ). Their formation has been tied to chromothripsis, as the long eccDNA contain a number of fragments from different parts of the genome.…”

Section: Introductionmentioning

confidence: 99%

MicroDNA levels are dependent on MMEJ, repressed by c-NHEJ pathway, and stimulated by DNA damage

Paulsen

Malapati

Shibata

et al. 2021

Nucleic Acids Research

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Extrachromosomal circular DNA (eccDNA) are present within all eukaryotic organisms and actively contribute to gene expression changes. MicroDNA (200-1000bp) are the most abundant type of eccDNA and can amplify tRNA, microRNA, and novel si-like RNA sequences. Due to the heterogeneity of microDNA and the limited technology to directly quantify circular DNA molecules, the specific DNA repair pathways that contribute to microDNA formation have not been fully elucidated. Using a sensitive and quantitative assay that quantifies eight known abundant microDNA, we report that microDNA levels are dependent on resection after double-strand DNA break (DSB) and repair by Microhomology Mediated End Joining (MMEJ). Further, repair of DSB without resection by canonical Non-Homologous End Joining (c-NHEJ) diminishes microDNA formation. MicroDNA levels are induced locally even by a single site-directed DSB, suggesting that excision of genomic DNA by two closely spaced DSB is not necessary for microDNA formation. Consistent with all this, microDNA levels accumulate as cells undergo replication in S-phase, when DNA breaks and repair are elevated, and microDNA levels are decreased if DNA synthesis is prevented. Thus, formation of microDNA occurs during the repair of endogenous or induced DNA breaks by resection-based DNA repair pathways.

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Molecular structure and evolution mechanism of two populations of double minutes in human colorectal cancer cells

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 11 publications

References 45 publications

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

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

Extrachromosomal circular DNA: a new potential role in cancer progression

MicroDNA levels are dependent on MMEJ, repressed by c-NHEJ pathway, and stimulated by DNA damage

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