You're using an outdated browser. Please upgrade to a modern browser for the best experience.
Submitted Successfully!
Thank you for your contribution! You can also upload a video entry or images related to this topic. For video creation, please contact our Academic Video Service.
Version Summary Created by Modification Content Size Created at Operation
1 Victoria Sanchez-Martin -- 1333 2023-02-06 12:42:20 |
2 Typo error Victoria Sanchez-Martin + 1 word(s) 1334 2023-02-06 12:44:20 | |
3 format correct Conner Chen + 57 word(s) 1391 2023-02-07 06:37:53 | |
4 format correct Conner Chen Meta information modification 1391 2023-02-07 06:38:30 | |
5 format correct Conner Chen + 3 word(s) 1394 2023-02-08 01:52:16 | |
6 format correct Conner Chen + 2 word(s) 1396 2023-02-08 02:22:33 |

Video Upload Options

We provide professional Academic Video Service to translate complex research into visually appealing presentations. Would you like to try it?
No, upload directly Yes
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Sanchez-Martin, V. Identification of DNA G-Guadruplexes. Encyclopedia. Available online: https://encyclopedia.pub/entry/40882 (accessed on 22 December 2025).
Sanchez-Martin V. Identification of DNA G-Guadruplexes. Encyclopedia. Available at: https://encyclopedia.pub/entry/40882. Accessed December 22, 2025.
Sanchez-Martin, Victoria. "Identification of DNA G-Guadruplexes" Encyclopedia, https://encyclopedia.pub/entry/40882 (accessed December 22, 2025).
Sanchez-Martin, V. (2023, February 06). Identification of DNA G-Guadruplexes. In Encyclopedia. https://encyclopedia.pub/entry/40882
Sanchez-Martin, Victoria. "Identification of DNA G-Guadruplexes." Encyclopedia. Web. 06 February, 2023.
Identification of DNA G-Guadruplexes
Edit
This entry is adapted from the peer-reviewed paper 10.3390/dna3010001

DNA G-quadruplexes (G4s) are non-canonical secondary structures formed in guanine-rich sequences. Within the human genome, G4s are found in regulatory regions such as gene promoters and telomeres to control replication, transcription, and telomere lengthening. In the cellular context, there are several proteins named as G4-binding proteins (G4BPs) that interact with G4s, either anchoring upon, stabilizing, and/or unwinding them.

G-quadruplex binding proteins

1. Introduction

DNA can adopt alternative secondary structures beyond the double helix. In G‐tetrads, four guanine bases are arranged via Hoogsteen base pairing in planar tetrameric squares. Several G‐tetrads, that are proximally located, self‐stack by π–π interactions further stabilized by monovalent or divalent cations centrally coordinated to form a three‐dimensional structure, termed as a G‐quadruplex (G4) [1]. G4s comprise several polymorphic structures and can fold into various topologies depending on the relative direction of the strands (i.e., parallel, antiparallel, or hybrid), the number of strands involved (i.e., intra or intermolecular), and the number of stacking G‐tetrads [2]. Within the genome, G4s are not randomly distributed. Instead, G4s are clustered in key regulatory sites such as gene promoters and telomeres, as well as in gene bodies [3]. Interestingly, nucleosome‐depleted regions and promoters of actively transcribed genes are significantly enriched in G4s [4]. Altogether, these observations strongly support their close involvement in functions of the genome including DNA replication, transcription, and epigenetic modification [5].

The participation of proteins is inherently required for the regulation of G4 formation across the whole genome and transcriptome, as well as the fulfillment of their biological functions. The proteins that specifically bind to G4s are known as G4‐binding proteins (G4BPs). The interest in G4BPs is considerably increasing for drug development owing to the ability to target the respective downstream processes directed by the interaction between G4BPs and the G4 counterpart.

2. G4BPs

The nucleic acid G4‐interacting proteins database (G4IPDB) contains comprehensive and updated information about proteins interacting with G4s [6]. At a freely accessible platform, G4IPDB includes more than 100 entries with data about interacting proteins, target sequence, PubMed reference number and binding details if available. Whilst there are multiple studies describing G4‐G4BP interactions, the functional outcome remains to be determined for many pairings [7].

The categorization of G4BPs is attainable in several ways. Firstly, G4BPs are divided into the following two types according to the distribution of G4s in the genome: (i) DNA and (ii) RNA G4BPs. The following contents only covers DNA G4BPs. Secondly, G4BPs are classified into two main types based on their functional relationships with G4s: (i) G4BPs that are recruited by G4s without affecting their structure and (ii) G4BPs that have an effect on the G4 structure. These last G4BPs are also divided into the following two categories in consonance with the structural effects on G4 structure: (i) G4‐stabilizing, which promote putative G4 sequences to form a stable G4 structure and (ii) G4‐destabilizing, which have the ability to unfold G4s.

Table 1 summarize recent discoveries related to the involvement of G4BPs in the regulation of cellular processes that include telomere lengthening, replication, transcription, chromatin remodeling, and histone modification.

Table 1. G4BPs involved in telomere lengthening, replication, transcription, and chromatin remodeling and histone modification. List of all G4BPs (alphabetically sorted) grouped according to their biological function. Literature column shows the reference in which the protein was first described as a G4BP.

Biological Function Protein Name Literature
Telomere lengthening BLM [8]
CST [9]
DNA2 [10]
hnRNPA1 [11]
hTERT [12]
Pif1 [13]
POT1 [14]
RPA [15]
RTEL1 [16]
TLS/FUS [17]
TRF2 [18][19]
UP1 [20]
WRN [8]
Replication BLM [21]
BRCA1 [22]
DDX11 [23]
FANCJ [24]
Pif1 [25]
WRN [21]
Transcription GQN1 [26]
hnRNPA1 [27]
MAZ [28]
NM23-H2 [29]
Nucleolin [30]
Nucleophosmin [31]
SP1 [32]
TP53 [33][34]
XPB [35]
XPD [35]
YY1 [36]
Chromatin remodeling and histone modification ATRX [37]
BRD3 [38]
CTCF [39]
DNMT1 [40]
REST-LSD1 [41]
SMARCA4 [42]

3. Structural Properties of G4BPs

Although there is a limited number of high-resolution structures of G4BPs interacting with G4s available, it is assumed that binding can occur at the following sites: (i) top-stacking with the upper G-tetrads, (ii) groove-binding, (iii) loop-binding, or a combination of those modes. The different functions of G4BPs may be linked to the binding mode the protein assumes in interacting with a G4. For instance, a top-stacking binding mode would appear to be more practical for G4BPs that unwind multiple and different G4s. In contrast, G4BPs that are too selective towards G4s may function through loop-binding because the orientation and length of the loops vary among different G4s (with a similar barrel core). Finally, groove-binders display a particular conformation able to fit into a groove of the G4 [43]. Interestingly, binding of a G4BP to a G4 does not equate to functioning. It was demonstrated that PARP-1 (poly(ADP-ribose) polymerase 1) affinity for a G4 increased as the loop features were removed, but PARP-1 activation was no longer achieved [44].

Analyzing the amino acid composition and structural patterns of G4BPs provides further insights into G4-recognition mechanisms. G4BPs are enriched in shared domains or motifs that are established or predicted to function as binding regions. In particular, 77 human G4BPs shared a domain rich in glycine and arginine residues [45]. Such a highly conserved domain is termed the RGG (Arginine-Glycine-Glycine)/RG (Arginine-Glycine) motif or GAR (Glycine-Arginine-rich) domain and is composed of repeat sequences rich in RGG or RG [46]. The RGG domain is important in G4–protein interactions. For instance, the RGG motif in nucleolin is essential for the recognition of the CMYC G4 sequence and the promotion of G4 formation [47]. The pairs of interactions between amino acid residues in proteins and bases in DNA have been identified [48]. Within the RGG domain, the internal arrangement of RGG repeats and gap amino acids seem to play a more crucial role in the G4-binding mechanism than a critical number of RGG repeats [49]. Interestingly, the cold-inducible RNA-binding protein (CIRBP) was the first protein identified as a G4BP both in vitro and in cells from the exploration of the RGG motif [49]. In addition, proteins that bind oligonucleotides or oligosaccharides were observed to contain a particular motif named the oligonucleotide/oligosaccharide-binding (OB)-fold domain. OB-fold has a five-stranded β-sheet coiled to form a closed β-barrel [50]. For instance, the OB-fold domain is included in several G4BPs such as CST [9] and POT1 [51] and participates in G4 interaction.

4. Concluding Remarks

The large number and evolutive conservation of G4s point to their importance in biological functions. Since G4 structures are also a source of genomic instability, G4 formation has to be tightly controlled. In this sense, G4s are highly dynamic in vivo and their folding depends on the cell type and chromatin state. G4BPs participate in the stabilization or resolution of G4s. Thus, it is important to consider the G4 not as an isolated entity, but rather as a structure that exists as part of an interconnected network of other biomolecules, such as G4BPS, within living cells. To date, a broad spectrum of G4BPs has been identified, but there are some difficulties in the analysis of the G4 interactome. Firstly, the interaction in vitro may not confirm the existence of such an event in vivo due to the plasticity of G4 formation in distinct cellular contexts. Secondly, three-dimensional structures of G4-G4BP complexes are still sparse. However, given the development of methodologies for the identification of G4BPs, it can be suspected that the number of proteins with G4-binding specificity will be increased in the future. While some of the known G4BPs appear to function as “pan-binders”, others act in a more selective manner and with different affinity, which implies that selectivity is attainable. Despite several domains involved in the recognition of G4s having already been characterized, there may still be others to be deciphered. Determining the features of G4BPs will be helpful in eliciting the details necessary to rationally design selective binders. Therefore, improving the selectivity of G4 binders to minimize off-target effects in the host cell remains a challenge for the future. Undoubtedly, a critical step to activate or inactivate physiological or pathological pathways is the recognition and processing of G4s by G4BPs. In this regard, the extensive research on G4BPs will provide new targets for drug design and pave the way for novel therapeutic approaches in human diseases.

References

  1. Neidle, S.; Balasubramanian, S. Quadruplex Nucleic Acids; RSC Publishing: London, UK, 2006.
  2. Burge, S.; Parkinson, G.N.; Hazel, P.; Todd, A.K.; Neidle, S. Quadruplex DNA: Sequence, topology and structure. Nucleic Acids Res. 2006, 34, 5402–5415.
  3. Huppert, J.; Balasubramanian, S. G-quadruplexes in promoters throughout the human genome. Nucleic Acids Res. 2006, 35, 406–413.
  4. Haensel-Hertsch, R.; Beraldi, D.; Lensing, S.V.; Marsico, G.; Zyner, K.; Parry, A.; Di Antonio, M.; Pike, J.; Kimura, H.; Narita, M.; et al. G-quadruplex structures mark human regulatory chromatin. Nat. Genet. 2016, 48, 1267–1272.
  5. Spiegel, J.; Adhikari, S.; Balasubramanian, S. The Structure and Function of DNA G-Quadruplexes. Trends Chem. 2019, 2, 123–136.
  6. Mishra, S.K.; Tawani, A.; Mishra, A.; Kumar, A. G4IPDB: A database for G-quadruplex structure forming nucleic acid interacting proteins. Sci. Rep. 2016, 6, 38144.
  7. Sun, Z.-Y.; Wang, X.-N.; Cheng, S.-Q.; Su, X.-X.; Ou, T.-M. Developing Novel G-Quadruplex Ligands: From Interaction with Nucleic Acids to Interfering with Nucleic Acid-Protein Interaction. Molecules 2019, 24, 396.
  8. Wu, W.; Rokutanda, N.; Takeuchi, J.; Lai, Y.; Maruyama, R.; Togashi, Y.; Nishikawa, H.; Arai, N.; Miyoshi, Y.; Suzuki, N.; et al. HERC2 Facilitates BLM and WRN Helicase Complex Interaction with RPA to Suppress G-Quadruplex DNA. Cancer Res. 2018, 78, 6371–6385.
  9. Bhattacharjee, A.; Wang, Y.; Diao, J.; Price, C.M. Dynamic DNA binding, junction recognition and G4 melting activity underlie the telomeric and genome-wide roles of human CST. Nucleic Acids Res. 2017, 45, 12311–12324.
  10. Lin, W.; Sampathi, S.; Dai, H.; Liu, C.; Zhou, M.; Hu, J.; Huang, Q.; Campbell, J.; Shin-Ya, K.; Zheng, L.; et al. Mammalian DNA2 helicase/nuclease cleaves G-quadruplex DNA and is required for telomere integrity. EMBO J. 2013, 32, 1425–1439.
  11. Krüger, A.C.; Raarup, M.K.; Nielsen, M.; Kristensen, M.; Besenbacher, F.; Kjems, J.; Birkedal, V. Interaction of hnRNP A1 with telomere DNA G-quadruplex structures studied at the single molecule level. Eur. Biophys. J. 2010, 39, 1343–1350.
  12. Paudel, B.P.; Moye, A.L.; Assi, H.A.; El-Khoury, R.; Cohen, S.B.; Holien, J.K.; Birrento, M.L.; Samosorn, S.; Intharapichai, K.; Tomlinson, C.G.; et al. A mechanism for the extension and unfolding of parallel telomeric g-quadruplexes by human telomerase at single-molecule resolution. Elife 2020, 9, e56428.
  13. Byrd, A.K.; Bell, M.R.; Raney, K.D. Pif1 helicase unfolding of G-quadruplex DNA is highly dependent on sequence and reaction conditions. J. Biol. Chem. 2018, 293, 17792–17802.
  14. Ray, S.; Bandaria, J.N.; Qureshi, M.H.; Yildiz, A.; Balci, H. G-quadruplex formation in telomeres enhances POT1/TPP1 protection against RPA binding. Proc. Natl. Acad. Sci. USA 2014, 111, 2990–2995.
  15. Qureshi, M.H.; Ray, S.; Sewell, A.L.; Basu, S.; Balci, H. Replication Protein A Unfolds G-Quadruplex Structures with Varying Degrees of Efficiency. J. Phys. Chem. 2012, 8, 5588–5594.
  16. Vannier, J.-B.; Sandhu, S.; Petalcorin, M.I.; Wu, X.; Nabi, Z.; Ding, H.; Boulton, S.J. RTEL1 is a replisome-associated helicase that promotes telomere and genome-wide replication. Science 2013, 342, 239–242.
  17. Takahama, K.; Takada, A.; Tada, S.; Shimizu, M.; Sayama, K.; Kurokawa, R.; Oyoshi, T. Regulation of telomere length by G-quadruplex telomere DNA- and TERRA-binding protein TLS/FUS. Chem. Biol. 2013, 20, 341–350.
  18. Biffi, G.; Tannahill, D.; Balasubramanian, S. An intramolecular G-quadruplex structure is required for binding of telomeric repeat-containing RNA to the telomeric protein TRF2. J. Am. Chem. Soc. 2012, 134, 11974–11976.
  19. Purohit, G.; Mukherjee, A.K.; Sharma, S.; Chowdhury, S. Extratelomeric Binding of the Telomere Binding Protein TRF2 at the PCGF3 Promoter Is G-Quadruplex Motif-Dependent. Biochemistry 2018, 57, 2317–2324.
  20. Hudson, J.S.; Ding, L.; Le, V.; Lewis, E.; Graves, D. Recognition and Binding of Human Telomeric G-Quadruplex DNA by Unfolding Protein 1. Biochemistry 2014, 53, 3347–3356.
  21. Sauer, M.; Paeschke, K. G-quadruplex unwinding helicases and their function in vivo. Biochem. Soc. Trans. 2017, 45, 1173–1182.
  22. Brázda, V.; Hároníková, L.; Liao, J.C.C.; Fridrichová, H.; Jagelská, E. Strong preference of BRCA1 protein to topologically constrained non-B DNA structures. BMC Mol. Biol. 2016, 17, 14.
  23. Guo, M.; Hundseth, K.; Ding, H.; Vidhyasagar, V.; Inoue, A.; Nguyen, C.H.; Zain, R.; Lee, J.S.; Wu, Y. A distinct triplex DNA unwinding activity of ChlR1 helicase. J. Biol. Chem. 2015, 290, 5174–5189.
  24. Castillo Bosch, P.; Segura-Bayona, S.; Koole, W.; Heteren, J.T.; Dewar, J.M.; Tijsterman, M.; Knipscheer, P. FANCJ promotes DNA synthesis through G-quadruplex structures. EMBO J. 2014, 33, 2521–2533.
  25. Paeschke, K.; Bochman, M.L.; Daniela Garcia, P.; Cejka, P.; Friedman, K.L.; Kowalczykowski, S.C.; Zakian, V.A. Pif1 family helicases suppress genome instability at G-quadruplex motifs. Nature 2013, 497, 458–464.
  26. Sun, H.; Yabuki, A.; Maizels, N. A human nuclease specific for G4 DNA. Proc. Natl. Acad. Sci. USA 2001, 98, 12444–12449.
  27. Xodo, L.; Paramasivam, M.; Membrino, A.; Cogoi, S. Protein hnRNPA1 binds to a critical G-rich element of KRAS and unwinds G-quadruplex structures: Implications in transcription. Nucleic Acids Symp. Ser. 2008, 52, 159–160.
  28. Cogoi, S.; Paramasivam, M.; Membrino, A.; Yokoyama, K.K.; Xodo, L.E. The KRAS promoter responds to Myc-associated zinc finger and poly(ADP-ribose) polymerase 1 proteins, which recognize a critical quadruplex-forming GA-element. J. Biol. Chem. 2010, 285, 22003–22016.
  29. Krishna Thakur, R.; Kumar, P.; Halder, K.; Verma, A.; Kar, A.; Parent, J.-L.; Basundra, R.; Kumar, A.; Chowdhury, S.; Ramachandran, G.N. Metastases suppressor NM23-H2 interaction with G-quadruplex DNA within c-MYC promoter nuclease hypersensitive element induces c-MYC expression. Nucleic Acids Res. 2009, 37, 172–183.
  30. González, V.; Guo, K.; Hurley, L.; Sun, D. Identification and characterization of nucleolin as a c-myc G-quadruplex-binding protein. J. Biol. Chem. 2009, 284, 23622–23635.
  31. Scognamiglio, P.L.; Di Natale, C.; Leone, M.; Poletto, M.; Vitagliano, L.; Tell, G.; Marasco, D. G-quadruplex DNA recognition by nucleophosmin: New insights from protein dissection. Biochim. Biophys. Acta Gen. Subj. 2014, 1840, 2050–2059.
  32. Raiber, E.A.; Kranaster, R.; Lam, E.; Nikan, M.; Balasubramanian, S. A non-canonical DNA structure is a binding motif for the transcription factor SP1 in vitro. Nucleic Acids Res. 2012, 40, 1499–1508.
  33. Quante, T.; Otto, B.; Brázdová, M.; Kejnovská, I.; Deppert, W.; Tolstonog, G.V. Mutant p53 is a transcriptional co-factor that binds to G-rich regulatory regions of active genes and generates transcriptional plasticity. Cell Cycle 2012, 11, 3290–3303.
  34. Petr, M.; Helma, R.; Polášková, A.; Krejčí, A.; Dvořáková, Z.; Kejnovská, I.; Navrátilová, L.; Adámik, M.; Vorlíčková, M.; Brázdová, M. Wild-type p53 binds to MYC promoter G-quadruplex. Biosci. Rep. 2016, 36, 397.
  35. Gray, L.T.; Vallur, A.C.; Eddy, J.; Maizels, N. G quadruplexes are genomewide targets of transcriptional helicases XPB and XPD. Nat. Chem. Biol. 2014, 10, 313–318.
  36. Li, L.; Williams, P.; Ren, W.; Wang, M.Y.; Gao, Z.; Miao, W.; Huang, M.; Song, J.; Wang, Y. YY1 interacts with guanine quadruplexes to regulate DNA looping and gene expression. Nat. Chem. Biol. 2020, 17, 161–168.
  37. Law, M.J.; Lower, K.M.; Voon, H.P.J.; Hughes, J.R.; Garrick, D.; Viprakasit, V.; Mitson, M.; De Gobbi, M.; Marra, M.; Morris, A.; et al. ATR-X syndrome protein targets tandem repeats and influences allele-specific expression in a size-dependent manner. Cell 2010, 143, 367–378.
  38. Pavlova, I.I.; Tsvetkov, V.B.; Isaakova, E.A.; Severov, V.V.; Khomyakova, E.A.; Lacis, I.A.; Lazarev, V.N.; Lagarkova, M.A.; Pozmogova, G.E.; Varizhuk, A.M. Transcription-facilitating histone chaperons interact with genomic and synthetic G4 structures. Int. J. Biol. Macromol. 2020, 160, 1144–1157.
  39. Tikhonova, P.; Pavlova, I.; Isaakova, E.; Tsvetkov, V.; Bogomazova, A.; Vedekhina, T.; Luzhin, A.V.; Sultanov, R.; Severov, V.; Klimina, K.; et al. DNA G-quadruplexes contribute to CTCF recruitment. Int. J. Mol. Sci. 2021, 22, 7090.
  40. Mao, S.Q.; Ghanbarian, A.T.; Spiegel, J.; Martínez Cuesta, S.; Beraldi, D.; Di Antonio, M.; Marsico, G.; Hänsel-Hertsch, R.; Tannahill, D.; Balasubramanian, S. DNA G-quadruplex structures mold the DNA methylome. Nat. Struct. Mol. Biol. 2018, 25, 951–957.
  41. Saha, D.; Singh, A.; Hussain, T.; Srivastava, V.; Sengupta, S.; Kar, A.; Dhapola, P.; Dhople, V.; Ummanni, R.; Chowdhury, S. Epigenetic suppression of human telomerase (hTERT) is mediated by the metastasis suppressor NME2 in a G-quadruplex-dependent fashion. J. Biol. Chem. 2017, 292, 15205–15215.
  42. Zhang, X.; Spiegel, J.; Cuesta, S.M.; Adhikari, S.; Balasubramanian, S. Chemical profiling of DNA G- quadruplex-interacting proteins in live cells. Nat. Chem. 2021, 13, 626–633.
  43. Meier-Stephenson, V. G4-quadruplex-binding proteins: Review and insights into selectivity. Biophys. Rev. 2022, 14, 635–654.
  44. Edwards, A.D.; Marecki, J.C.; Byrd, A.K.; Gao, J.; Raney, K.D. G-Quadruplex loops regulate PARP-1 enzymatic activation. Nucleic Acids Res. 2021, 49, 416–431.
  45. Brázda, V.; Červeň, J.; Bartas, M.; Mikysková, N.; Coufal, J.; Pečinka, P. The Amino Acid Composition of Quadruplex Binding Proteins Reveals a Shared Motif and Predicts New Potential Quadruplex Interactors. Molecules 2018, 23, 2341.
  46. Thandapani, P.; O’Connor, T.R.; Bailey, T.L.; Richard, S. Defining the RGG/RG Motif. Mol. Cell 2013, 50, 613–623.
  47. González, V.; Hurley, L.H. The C-Terminus of Nucleolin Promotes the Formation of the c-MYC G-Quadruplex and Inhibits c-MYC Promoter Activity. Biochemistry 2010, 49, 9706–9714.
  48. Sathyapriya, R.; Vishveshwara, S. Interaction of DNA with clusters of amino acids in proteins. Nucleic Acids Res. 2004, 32, 4109–4118.
  49. Huang, Z.-L.; Dai, J.; Luo, W.-H.; Wang, X.-G.; Tan, J.-H.; Chen, S.-B.; Huang, Z.-S. Identification of G-Quadruplex-Binding Protein from the Exploration of RGG Motif/G-Quadruplex Interactions. J. Am. Chem. Soc. 2018, 140, 17945–17955.
  50. Murzin, A.G. OB(oligonucleotide/oligosaccharide binding)-fold: Common structural and functional solution for non-homologous sequences. EMBO J. 1993, 12, 861–867.
  51. Hwang, H.; Buncher, N.; Opresko, P.L.; Myong, S. POT1-TPP1 regulates telomeric overhang structural dynamics. Structure 2012, 20, 1872–1880.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Biochemistry & Molecular Biology
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register : Victoria Sanchez-Martin
View Times: 726
Revisions: 6 times (View History)
Update Date: 08 Feb 2023
Table of Contents
    Notice
    You are not a member of the advisory board for this topic. If you want to update advisory board member profile, please contact office@encyclopedia.pub.
    OK
    Confirm
    Only members of the Encyclopedia advisory board for this topic are allowed to note entries. Would you like to become an advisory board member of the Encyclopedia?
    Yes
    No
    ${ textCharacter }/${ maxCharacter }
    Submit
    Cancel
    There is no comment~
    ${ textCharacter }/${ maxCharacter }
    Submit
    Cancel
    ${ selectedItem.replyTextCharacter }/${ selectedItem.replyMaxCharacter }
    Submit
    Cancel
    Confirm
    Are you sure to Delete?
    Yes No
    Academic Video Service
    Feedback