By Natalie Tan
Definitions:
in vivo(1) - “(of a process) performed or taking place in a living organism.”
HeLa cells(2) - “is an immortal cell line used in scientific research,” one that is “named after and derived from cervical cancer cells taken on February 8, 1951, from Henrietta Lacks.”
NMR spectroscopy(3) - “as an indispensable tool which applies a magnetic field to an atomic nucleus.”
S-phase(4) - “is the Synthesis Phase, the phase of the cell cycle in which DNA is replicate(d).”
transcription(5) - “the process of transcribing RNA, with existing DNA serving as a template.”
G1 phase(6) - “G1 is the phase when this cellular monitoring takes place.”
If you had to guess what the words “Intercalated Motif” meant, would you have thought of DNA? That’s right. Intercalated Motif, also known as I-Motif, is part of the DNA family. Now you are probably picturing the standard double helix. However, that is not the case. I-motif structures, in contrast to double-stranded DNA (duplex DNA), are four-stranded DNA structures that consists of two parallel-stranded duplexes intercalated in an antiparallel orientation (Abou Assi, Hala, et al., 2018).
Intercalated motif structures were actually first observed about 28 years ago. At first, many dismissed it as a “structural oddity”. As a result, there wasn’t a lot of research being done about them. Uncertainty about the in vivo(1) existence of i-motif structures due to a lack of research persisted until a recent visualization, using antibody fragments, recognized i-motif structures in a structure-specific manner (Abou Assi, Hala, et al., 2018).
This revelation contributed to the conclusion that Intercalated Motif structures may have been formed in “regulatory regions of the human genome,” and play an important role in regulating gene expression (Abou Assi, Hala, et al., 2018).
Due to a lack of experimental evidence, the biological relevance of Intercalated Motif structures has been highly questioned. Nonetheless, a study performed by Dzatko et al (as cited in Abou Assi et al., 2018) changed this ideology. They found that pre-formed i-motif structures sustained stability when introduced into the environment of living HeLa cells(2) by applying NMR spectroscopy(3) to living cells. This demonstrated how stable these structures are.
In another study conducted by Christ’s and Dinger’s groups, they developed an antibody. An antibody that had the ability to bind with C-rich DNA sequences, forming Intercalated Motif structures. The results of this investigation showed that the number of Intercalated Motif structures in the nuclei of cells varied along the cell cycle. The majority of Intercalated Motif structures present in cells during the cell cycle were found in the S-phase(4). This discovery suggests that the “i-motif formation can be associated with transcription(5) as late G1 phase(6) is characterized by high transcriptional activity.”
Now you may be wondering what these two breakthroughs mean for the future of cellular biology.
In spite of the many developments about Intercalated Motif structures in recent years, more in vivo studies are necessary to confirm the conclusions that have been made about these structures and their roles in different biological processes. Due to the ideas that Intercalated Motif structures are stable and are most likely associated with transcription, scientists believe that Intercalated Motif structures “may play a role in causing cancer and degenerative diseases in humans” (DNewsChannel, 2016, 3:22). This means that a better understanding of Intercalated Motif could mean the cure for cancer and other genetic disorders.
References
Abou Assi, Hala, et al. “I-Motif DNA: Structural Features and Significance to Cell Biology.” Nucleic Acids Research, Oxford University Press, 19 Sept. 2018, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6144788/.
Day, Henry A., et al. “I-Motif DNA: Structure, Stability and Targeting with Ligands.” Bioorganic & Medicinal Chemistry, Pergamon, 4 June 2014, https://www.sciencedirect.com/science/article/abs/pii/S0968089614004064.
DNewsChannel, Seeker, director. What Is 4-Strand DNA & Why Are Scientists So Excited? YouTube, YouTube, 9 June 2016, https://www.youtube.com/watch?v=s_5FRaQ8YM4. Accessed 11 Oct. 2021.
Dzatko, Simon, et al. “Evaluation of the Stability of DNA I-Motifs in the Nuclei of Living Mammalian Cells.” Angewandte Chemie (International Ed. in English), John Wiley and Sons Inc., 19 Feb. 2018, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5820743/.
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