G-quadruplex-interacting compounds alter latent DNA replication and episomal persistence of KSHV

Madireddy, Advaitha; Purushothaman, Pravinkumar; Loosbroock, Christopher; Robertson, Erle S.; Schildkraut, Carl L.; Verma, Subhash C.

doi:10.1093/nar/gkw038

Cited by 71 publications

(76 citation statements)

References 66 publications

(81 reference statements)

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“…SMARD analysis was carried our using a procedure described previously (Madireddy et al, 2016; Norio and Schildkraut, 2001)(Gerhardt et al, 2014). Briefly, exponentially growing cells were cultured in media containing 30 µM 5-iodo-2′-deoxyuridine (IdU) at 37°C for 4 h (Sigma-Aldrich, St. Louis, MO).…”

Section: Methodsmentioning

confidence: 99%

FANCD2 Facilitates Replication through Common Fragile Sites

et al. 2016

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SUMMARY Common fragile sites (CFSs) are genomic regions that are unstable under conditions of replicative stress. Although the characteristics of CFSs that render them vulnerable to stress are mainly associated with replication, the cellular pathways that protect CFSs during replication remain unclear. Here, we identify and describe a role for FANCD2 as a trans-acting facilitator of CFS replication, in the absence of exogenous replicative stress. In the absence of FANCD2, replication forks stall within the AT-rich fragility core of CFS leading to dormant origin activation. Furthermore, FANCD2 deficiency is associated with DNA:RNA hybrid formation at CFS-FRA16D and inhibition of DNA:RNA hybrid formation suppresses replication perturbation. In addition, we also found that FANCD2 reduces the number of potential sites of replication initiation. Our data demonstrate that FANCD2 protein is required to ensure efficient CFS replication and provide mechanistic insight into how FANCD2 regulates CFS stability.

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Section: Methodsmentioning

confidence: 99%

FANCD2 Facilitates Replication through Common Fragile Sites

et al. 2016

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“…Particularly, G-quadruplexes are found in genomes of human pathogens [144]. Many examples of G-quadruplexes were identified in viruses [145,146], including human immunodeficiency virus (HIV) [147][148][149][150], multiple species of herpes virus [151][152][153][154][155], human papillomavirus (HPV) [156], hepatitis C [157], Zika [158], Ebola [159], and a G-quadruplexbinding protein was found in severe acute respiratory syndrome (SARS) coronavirus [160]. In bacteria, G-quadruplexes are found in Escherichia coli [161], Neisseria gonorrhoeae [162], Neisseria meningitidis [163], Mycobacterium tuberculosis [164], and Deinococcus radiodurans [165].…”

Section: G-quadruplexes In Nonhuman Genomesmentioning

confidence: 99%

G-Quadruplex DNA and RNA

Yang

2019

Methods in Molecular Biology

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G-quadruplexes (G4s) have become one of the most exciting nucleic acid secondary structures. A noncanonical, four-stranded structure formed in guanine-rich DNA and RNA sequences, G-quadruplexes can readily form under physiologically relevant conditions and are globularly folded structures. DNA is widely recognized as a double-helical structure essential in genetic information storage. However, only~3% of the human genome is expressed in protein; RNA and DNA may form noncanonical secondary structures that are functionally important. G-quadruplexes are one such example which have gained considerable attention for their formation and regulatory roles in biologically significant regions, such as human telomeres, oncogene-promoter regions, replication initiation sites, and 5 0 -and 3 0 -untranslated region (UTR) of mRNA. They are shown to be a regulatory motif in a number of critical cellular processes including gene transcription, translation, replication, and genomic stability. G-quadruplexes are also found in nonhuman genomes, particularly those of human pathogens. Therefore, G-quadruplexes have emerged as a new class of molecular targets for drug development. In addition, there is considerable interest in the use of G-quadruplexes for biomaterials, biosensors, and biocatalysts. The First International Meeting on Quadruplex DNA was held in 2007, and the G-quadruplex field has been growing dramatically over the last decade. The methods used to study G-quadruplexes have been essential to the rapid progress in our understanding of this exciting nucleic acid secondary structure. G-quadruplexes have been found to form in specific human guanine-rich sequences with functional significance, such as telomeres, oncogene-promoter regions, and 5 0 -and 3 0 -untranslated region (UTR) of mRNA, as well as in nonhuman genomes. G-Quadruplexes in TelomeresThe first biologically relevant G-quadruplex was observed in telomeric DNA. Telomeres are specific DNA-protein complexes at the ends of linear chromosomes, providing protection against gene erosion from cell divisions, chromosomal nonhomologous end-joinings, and nuclease attacks [19][20][21]. Telomeric G-quadruplexes were first reported as novel intramolecular structures containing guanine-guanine base-pairs in single-stranded telomeric sequences of several organisms [22], and as guaninetetrads between hairpin loops of the Tetrahymena telomeric DNA [23]. The importance of monovalent cations in the stabilization of G-quadruplex structures was revealed by Williamson, Cech in their monovalent cation-induced square-planar G-quartet model using the Oxytricha and Tetrahymena telomeric DNA [14]. Human telomeres consist of tandem repeats of the hexanucleotide d (TTAGGG) n 5-10 kb in length, which terminate in a singlestranded 3 0 -overhang of 35-600 bases [24]. Telomeres of cancer cells do not shorten upon replication, mainly due to the activation of a reverse transcriptase, telomerase, that extends the telomeric sequence at the chromosome ends [25]. Telomerase is activated in 80-85% of hu...

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“…Among the microorganisms that contain a G4 in their genome, the over-representation of viruses associated with cancer, namely, KSHV, EBV, HCV, HBV, and HPV, is noteworthy [40,51,60,63,76]. The existence of these secondary structures in zoonotic agents such as Ebola virus and vector-borne pathogens such as Zika virus, Plasmodium spp., B. burgdorferi, and T. brucei, is particularly interesting [24,42,93,94].…”

Section: Discussionmentioning

confidence: 99%

“…KSHV is an oncogenic virus that has acquired a number of its genes by molecular piracy. The terminal repeat (TR) region of KSHV genome is enriched for quadruplex-forming sequence motifs with each repetitive element (about 800 bp), having 12 and 16 putative quadruplexforming sequences in the top and the bottom strand respectively [60]. The TR region harbours the only origin for replication of viral episomes.…”

Section: Role In Virus Latencymentioning

confidence: 99%

G-Quadruplexes: More Than Just a Kink in Microbial Genomes

Saranathan

Vivekanandan

2019

Trends in Microbiology

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G-quadruplexes (G4s) are noncanonical nucleic acid secondary structures formed by guanine-rich DNA and RNA sequences. In this review we aim to provide an overview of the biological roles of G4s in microbial genomes with emphasis on recent discoveries. G4s are enriched and conserved in the regulatory regions of microbes, including bacteria, fungi, and viruses. Importantly, G4s in hepatitis B virus (HBV) and hepatitis C virus (HCV) genomes modulate genes crucial for virus replication. Recent studies on Epstein-Barr virus (EBV) shed light on the role of G4s within the microbial transcripts as cis-acting regulatory signals that modulate translation and facilitate immune evasion. Furthermore, G4s in microbial genomes have been linked to radioresistance, antigenic variation, recombination, and latency. G4s in microbial genomes represent novel therapeutic targets for antimicrobial therapy.

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G-quadruplex-interacting compounds alter latent DNA replication and episomal persistence of KSHV

Cited by 71 publications

References 66 publications

FANCD2 Facilitates Replication through Common Fragile Sites

FANCD2 Facilitates Replication through Common Fragile Sites

G-Quadruplex DNA and RNA

G-Quadruplexes: More Than Just a Kink in Microbial Genomes

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