Mitotic clustering of pulverized chromosomes from micronuclei

Lin, Yu‐Fen; Valle-Inclán, Jose Espejo; Mazzagatti, Alice; Hu, Qing; Maurais, Elizabeth G; Guyer, Alison; Sanders, Jacob T; Engel, Justin L.; Nguyen, Giaochau; Bronder, Daniel; Bakhoum, Samuel F.; Cortés-Ciriano, Isidro; Ly, Peter

doi:10.1101/2022.07.19.500697

Cited by 4 publications

(4 citation statements)

References 53 publications

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“…Chromothripsis ( cth ) is a phenomenon by which hundreds of rearrangements originate through random shattering and reshuffling of clustered chromosome regions within a single catastrophic event. The predominant method of reassembly of the shattered pieces is classical non-homologous end joining (C-NHEJ) [6‒8]. ogm (2p)cth…”

Section: Resultsmentioning

confidence: 99%

Genome Mapping Nomenclature

Moore,

McGowan-Jordan,

Smith

et al. 2023

Cytogenet Genome Res

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Background Genome Mapping Technologies (optical and electronic) uses ultra high-molecular weight DNA to detect structural variation and has an application in constitutional genetic disorders, haematological neoplasms and solid tumours. Genome mapping can detect balanced and unbalanced structural variation, copy number changes and haplotypes. The technique is analogous to chromosomal microarray analysis although genome mapping has the added benefit of being able to detect and ascertain the nature of more abnormalities than array, karyotyping or FISH. Key Messages This paper describes a specific nomenclature for genome mapping that can be used by diagnostic and research centres to accurately report their findings. An international nomenclature is essential for patient results to be understood by different healthcare providers as well as clear communication in publications and consistency in databases. Summary Genome mapping can detect aneuploidy, balanced and unbalanced structural variation as well as copy number changes. The Standing Committee for the International System for Human Cytogenomic Nomenclature (ISCN), recognised there was a need for a specific nomenclature for genome mapping that encompasses the range of abnormalities detected by this technique. This paper explains the general principles of the nomenclature as well as giving specific ISCN examples for the different types of numerical and structural rearrangements.

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Section: Resultsmentioning

confidence: 99%

Genome Mapping Nomenclature

Moore,

McGowan-Jordan,

Smith

et al. 2023

Cytogenet Genome Res

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“…One feature that contributes to hotspots of HPV DNA integration are common and cell‐type specific chromosomal fragile sites, which can develop DBS during replication stress which also can lead to alteration in gene expression levels 20,82–84 . Recent studies have also found that HPV integration can occur at DBS associated with chromothripsis, which as previously mentioned can generate genome‐wide chromosomal changes and have MHS at repair junctions 85–88 . Integration next to coding regions or even distant flanking regions of genes can lead to changes like amplification, rearrangement, translocation, or long‐range cis interactions.…”

Section: Mechanisms Of Microhomology‐mediated Dna Repair Machinery In...mentioning

confidence: 99%

Microhomology‐mediated repair machinery and its relationship with HPV‐mediated oncogenesis

Chatterjee,

Starrett

2024

Journal of Medical Virology

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Human Papillomaviruses (HPV) are a diverse family of non‐enveloped dsDNA viruses that infect the skin and mucosal epithelia. Persistent HPV infections can lead to cancer frequently involving integration of the virus into the host genome, leading to sustained oncogene expression and loss of capsid and genome maintenance proteins. Microhomology‐mediated double‐strand break repair, a DNA double‐stranded breaks repair pathway present in many organisms, was initially thought to be a backup but it's now seen as vital, especially in homologous recombination‐deficient contexts. Increasing evidence has identified microhomology (MH) near HPV integration junctions, suggesting MH‐mediated repair pathways drive integration. In this comprehensive review, we present a detailed summary of both the mechanisms underlying MH‐mediated repair and the evidence for its involvement in HPV integration in cancer. Lastly, we highlight the involvement of these processes in the integration of other DNA viruses and the broader implications on virus lifecycles and host innate immune response.

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“…TopBP1 is an active protein during mitosis and is critical for maintaining genome integrity (16,(34)(35)(36)(37)(38)(39)(40)(41)(42)(43). The ability of E2-K111Q to remove TopBP1 from mitotic chromatin indicated this protein may disrupt mitosis.…”

Section: Lysine Mutations In E2 Disrupt E2 Mitotic Interaction and Ab...mentioning

confidence: 99%

A human papillomavirus 16 E2-TopBP1 dependent SIRT1-p300 acetylation switch regulates mitotic viral and human protein levels

Prabhakar,

James,

Youssef

et al. 2024

Preprint

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An interaction between human papillomavirus 16 (HPV16) E2 and the cellular proteins TopBP1 and BRD4 is required for E2 plasmid segregation function. The E2-TopBP1 interaction promotes increased mitotic E2 protein levels in U2OS and N/Tert-1 cells, as well as in human foreskin keratinocytes immortalized by HPV16 (HFK+HPV16). SIRT1 deacetylation reduces E2 protein stability and here we demonstrate that increased E2 acetylation occurs during mitosis in a TopBP1 interacting dependent manner, promoting E2 mitotic stabilization. p300 mediates E2 acetylation and acetylation is increased due to E2 switching off SIRT1 function during mitosis in a TopBP1 interacting dependent manner, confirmed by increased p53 stability and acetylation on lysine 382, a known target for SIRT1 deacetylation. SIRT1 can complex with E2 in growing cells but is unable to do so during mitosis due to the E2-TopBP1 interaction; SIRT1 is also unable to complex with p53 in mitotic E2 wild type cells but can complex with p53 outside of mitosis. E2 lysines 111 and 112 are highly conserved residues across all E2 proteins and we demonstrate that K111 hyper-acetylation occurs during mitosis, promoting E2 interaction with Topoisomerase 1 (Top1). We also demonstrate that K112 ubiquitination promotes E2 proteasomal degradation during mitosis. The results present a model in which the E2-TopBP1 complex inactivates SIRT1 during mitosis and E2 acetylation on K111 by p300 increases, promoting interaction with Top1 that protects K112 from ubiquitination and therefore E2 proteasomal degradation.

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Mitotic clustering of pulverized chromosomes from micronuclei

Cited by 4 publications

References 53 publications

Genome Mapping Nomenclature

Genome Mapping Nomenclature

Microhomology‐mediated repair machinery and its relationship with HPV‐mediated oncogenesis

A human papillomavirus 16 E2-TopBP1 dependent SIRT1-p300 acetylation switch regulates mitotic viral and human protein levels

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