The Choreography of Life: Proteins and DNA

Aneena Fran Kalarithara

Aneena Fran Kalarithara

— 5 min read

Unraveling the Molecular Conversations That Power Life

Proteins bound to the DNA double helix — a glimpse into molecular interactions. (Image created by the author using Sora).

For decades, scientists were convinced that proteins carried our heredity, not DNA.

Proteins were complex, glamorous, alive with function. DNA? Just a boring string of repeating units. The shock came when experiments flipped that assumption on its head.

It wasn’t until the 1940s and ’50s, through historical experiments like Avery–MacLeod–McCarty and Hershey–Chase, that DNA’s true role as the carrier of genetic information was revealed. And then, thanks to Watson, Crick, Franklin, and Wilkins, we finally got the famous double helix into the spotlight, forever changing the world of molecular biology.

But here’s the truth: studying DNA alone is like having just the singer in a band — no drums, no guitar, no violin. Sure, you’d hear the lyrics, but you’d miss the rhythm, harmony, and energy that makes the performance whole. Likewise, the real magic happens when the DNA and proteins are in a constant molecular conversation, one which decides if a gene gets read or if a protein gets expressed.

Meet the Cast of Proteins

To understand why protein–DNA interactions are so important, let’s look into some of the most fascinating players. We’ll start simple and build our way up.

Histones: The DNA Spools

Did you know? If you stretched out all the DNA in one of your cells, you’d get about two meters of thread. Yet, it somehow fits into a space smaller than a grain of salt. The magic trick? Histones.

Function: Histones act like spools, wrapping DNA around itself securing it in compact bundles called nucleosomes.

DNA coiled around histone proteins (nucleosome), enabling tight packaging and gene control (Caputi, Candeletti & Romualdi, 2017).

Importance: Histones aren’t just storage containers — they also control access. Whether or not if the DNA gets read depends on how tightly the DNA is bound around the histone. Genes wrapped too tightly stay hidden; loosen the wrap, and the gene becomes readable. Through chemical modifications, histones help decide which parts of the genome are expressed and which remain silent.

Transcription Factors (TFs): The gene switches

If histones are the storage cases for DNA, then transcription factors are the conductors of the orchestra. They don’t play an instrument themselves, but without them, the music would dissolve into noise. By signaling which musicians (genes) should come in and which should stay silent, transcription factors create order out of chaos.

Function: TFs bind to specific DNA sequences and decide whether to read the gene or not. They act like switches for gene activity to turn them ON or OFF.

Transcription factors act like molecular switches — some turn genes on (green arrow), while others block them (red bar). Here, they regulate miR-29 expression.( Amodio et al., 2015, Oncotarget)

Importance: Without TFs, cells wouldn’t know when to divide or self - destruct itself in the case of damaged cells.

For example, p53 - also renamed as the “guardian of the genome” - binds to DNA to trigger repair or cell death if damage is detected. The p53 malfunctioning can be a critical issue and can cause diseases such as cancer.

The precision of transcription factors prevents dangerous mistakes: hydrochloric acid is confined to the stomach where it belongs, and liver cells never take on the identity of neurons.

 DNA & RNA Polymerases: The Copy Machines

Every time your cells divide, they must copy about 6 billion letters of DNA with near-perfect accuracy. And when genes need to be read, mRNA has to be made on demand.

Function:

  • DNA polymerases copy DNA during replication.
  • RNA polymerases transcribe DNA into RNA, the working instructions of the cell. This flow of information — DNA → RNA → Protein — is known as the central dogma of molecular biology. It’s the core principle that explains how genetic information is ultimately turned into functional proteins that keep us alive.
“RNA polymerase unwinds DNA and builds an RNA strand by reading the template one base at a time.”(Source: Technology Networks)

Importance: Polymerases aren’t just copy machines, they’re proofreaders as well. DNA polymerases catch typos that could lead to dangerous mutations, while RNA polymerases make sure the right messages are delivered to the right place at the right time.

Fun Fact: In Escherichia coli, the main replication enzyme, DNA Polymerase III, can synthesize DNA at speeds approaching 1,000 nucleotides per second.

Nucleolin: The Hidden Player

Nucleolin may not be as famous as p53, but it’s a rising star in cancer research.

Function: Nucleolin helps in organizing and transcribing ribosomal RNA, which is needed to make ribosomes — the protein factories in cells.

3D structure of nucleolin from the Protein Data Bank (PDB)

Importance: In healthy cells nucleolin keeps ribosome production going. However, in many cancer cells nucleolin is over expressed which can support uncontrolled cell growth — a key characteristic of cancer.

Recently, researchers discovered that nucleolin can bind to G-quadruplexes (G4s) — proteins often found in the promoter regions/ telomeres — making it a potential target for cancer therapy.

Why Does This Matter?

Studying proteins alongside DNA isn’t just academic curiosity — it is essential. These protein–DNA interactions control everything from cell identity to disease prevention. When they go wrong, the results can be devastating, but when we understand them, we unlock strategies for therapies, gene editing, and much more.

References

1. Meier-Stephenson, V. (2022). G4-quadruplex-binding proteins: review and insights into selectivity. Biophysical Reviews, 14(3), 635–654. https://doi.org/10.1007/s12551-022-00952-8

2. DNA polymerase III holoenzyme. (n.d.). In Wikipedia. Retrieved from https://en.wikipedia.org/wiki/DNA_polymerase_III_holoenzyme

3. Caputi, F., Candeletti, S., & Romualdi, P. (2017). Epigenetic Approaches in Neuroblastoma Disease Pathogenesis. IntechOpen. https://doi.org/10.5772/intechopen.69566

4. Amodio, N., Rossi, M., Raimondi, L., Pitari, M., Botta, C., Tagliaferri, P., & Tassone, P. (2015). miR-29s: A family of epi-miRNAs with therapeutic implications in hematologic malignancies. Oncotarget, 6. https://doi.org/10.18632/oncotarget.3805

5. Abuetabh, Y., Wu, H. H., Chai, C., et al. (2022). DNA damage response revisited: the p53 family and its regulators provide endless cancer therapy opportunities. Experimental & Molecular Medicine, 54, 1658–1669. https://doi.org/10.1038/s12276-022-00863-4

6. DNA: A timeline of discoveries. (n.d.). BBC Science Focus. Retrieved from https://www.sciencefocus.com/the-human-body/dna-a-timeline-of-discoveries

7. Histone. Wikipedia. Retrieved August 17, 2025, from: https://en.wikipedia.org/wiki/Histone

Read more