BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: DNA repair

Unlocking the Secrets of Immortality: Bowhead Whales Defy Time and Cancer

When we look into nature, we often find remarkable solutions to some of our most pressing problems. From the camouflage skills of chameleons to the adhesive prowess of geckos, nature constantly astounds us with its ingenuity. Today, we’re diving into the fascinating world of bowhead whales, those majestic giants of the Arctic Ocean, and the incredible superpower hidden within their cells. Their unique DNA repair mechanisms might just be the key to unlocking groundbreaking advancements in cancer treatments for humans. But before we explore this potentially groundbreaking research, I want to share a personal connection to this topic. Whales, in particular, hold a special place in my heart—they are my favorite animals. This article resonates with my love for the ocean and its untapped potential to solve some of our most challenging medical puzzles, all thanks to a stuffed animal whale that was my cherished bedtime buddy!

I’m sure many of you also have a personal connection to the natural world or a favorite animal that has inspired your curiosity. Feel free to share your own stories or connections in the comments!

“Bowhead whales may have a cancer-defying superpower: DNA repair” by Meghan Rosen discusses the extraordinary longevity of bowhead whales, which can live for more than 200 years. Scientists have found that these whales possess a remarkable ability to repair damaged DNA, which could be the key to their cancer resistance.

A bowhead whale breaches off the coast of western Sea of Okhotsk by Olga Shpak, Marine Mammal Council, IEE RAS

The enormous size and large number of cells in the bowhead whale raise the possibility of cell mutations occurring during cell division, which in theory could raise the risk of cancer. A phenomenon known as Peto’s paradox states that large-bodied animals like bowhead whales appear to have robust cancer-prevention mechanisms that have evolved throughout time.

Bowhead whales appear to have a different technique from other huge mammals like elephants, which have additional copies of the tumor-blocking gene TP53 to get rid of damaged cells. Their cells are extremely effective at repairing double-strand DNA breaks, a type of damage that could cause cancer, as opposed to eliminating it. The less accurate DNA repair in other animals is contrasted with the effective repair process in bowhead whales.

It’s intriguing how different species have developed unique strategies to combat cancer. Share your thoughts on the varied approaches in the animal kingdom!

The study conducted by biologist Denis Firsanov and colleagues reveals that bowhead whale cells outperform human, mouse, and cow cells in repairing DNA damage, displaying an exceptionally efficient and accurate DNA repair system. The whales can tolerate more genomic damage because they possess a precise, rapid DNA repair mechanism. Moreover, bowhead whale cells produce higher levels of a DNA repair protein called CIRBP compared to other species studied. When human cells were engineered to produce bulk CIRBP, they exhibited improved DNA repair capabilities. The researchers conclude that the strategy of repairing damaged cells without eliminating them may be essential for the long, cancer-free lifespan of bowhead whales. Yale University cancer biologist Jason Sheltzer, though not involved in the research, finds this preprint fascinating, as it offers a new model for understanding how larger animals avoid cancer, possibly through superior DNA repair capabilities.

Dna-repair-12-638

It is very important to fully understand how animals, such as bowhead whales, defend themselves against cancer because it may one day be possible to develop cancer cures for mankind. The importance of finding nature’s cures for medical problems is highlighted by research on animals with low cancer rates, as these methods could revolutionize human healthcare.
In AP Bio Unit 1 this quarter, I have learned the fundamental importance of cells.  Like we talked about, cells have proteins. In the research, the study identified two specific proteins, CIRBP and RPA2, that play a role in the DNA repair mechanism of bowhead whale cells. These proteins contribute to the efficiency of the repair process.

How have your studies or interests in biology influenced your understanding of topics like DNA repair and cellular mechanisms? Share your insights!

While human cells have their own set of DNA repair proteins, the specific proteins and mechanisms in human cells may differ from those in bowhead whales, potentially leading to variations in repair efficiency. We also talked about the Endomembrane System, including the Golgi apparatus, which is responsible for the processing and transport of molecules within the cell. In the context of the article, efficient intracellular transport of repair proteins and DNA repair products within bowhead whale cells is essential for their cancer resistance. Additionally, lysosomes in the endomembrane system are responsible for cellular waste disposal. In the context of the article, understanding how bowhead whale cells efficiently repair damaged DNA is also linked to the concept of maintaining cellular integrity and reducing the need for cellular degradation and recycling.

New research further advances the understanding of DNA repair

In a study recently published in Nature Cell Biology, there’s been a discovery that alters our understanding of how the body’s DNA repair process works and may lead to new chemotherapy treatments for cancer and other disorders. Because DNA is the repository of genetic information in each living cell, its integrity and stability are essential to life. DNA, however, is not inert. Rather, it is a chemical entity subject to abuse from the environment and any resulting damage, if not repaired, will lead to mutation and possibly disease.

The fact that DNA can be repaired after it has been damaged is one of the great mysteries of medical science, but pathways involved in the repair process vary during different stages of the cell life cycle. In one of the repair pathways known as base excision repair (BER), the damaged material is removed, and a combination of proteins and enzymes work together to create DNA to fill in and then seal the gaps. In addition to genetic insults caused by the environment, the very process of DNA replication during cell division is prone to error. The rate at which DNA polymerase adds incorrect nucleotides during DNA replication is a major factor in determining the spontaneous mutation rate in an organism.

Researchers discovered that BER has a built-in mechanism to increase its effectiveness, it just needs to be captured at a very precise point in the cell life cycle. In BER, an enzyme called polymerase beta (PolyB) fulfills two functions: It creates DNA, and it initiates a reaction to clean up the leftover chemical waste. Through five years of study, scientists learned that by capturing PolyB when it is naturally cross-linked with DNA, the enzyme will create new genetic material at a speed 17 times faster than when the two are not cross-linked. This suggests that the two functions of PolyB are interlocked, not independent, during BER.

Cancer cells replicate at high speed, and their DNA endures a lot of damage. When a doctor uses certain drugs to attack cancer cells’ DNA, the cancer cells must cope with additional DNA damage. If the cancer cells cannot rapidly fix DNA damage, they will die. Otherwise, the cancer cells survive, and drug resistance appears. This research examined naturally cross-linked PolyB and DNA, unlike previous research that mimicked the process. Prior to this study, researchers had identified the enzymes involved in BER but didn’t fully understand how they work together. This research improves the understanding of cellular genomic stability, drug efficacy, and resistance associated with chemotherapy, which, as previously stated, can lead to new chemotherapy treatments for cancer and other disorders.

New Information on DNA Repair Could Mean Better Cancer Treatments

Photo Taken by EMW http://en.wikipedia.org/wiki/File:Protein_BRCA1_PDB_1jm7.png

Photo Taken by EMW http://en.wikipedia.org/wiki/File:Protein_BRCA1_PDB_1jm7.png

 

It has been accepted that DNA repairs itself.  However, a discovery concerning how this process occurs could lead to more efficient, and thus less damaging, cancer treatments.  Medical researchers at the University of Alberta have expanded the knowledge that scientists have regarding two proteins: BRCA1 (shown in the image) and TopBP1.  These proteins were previously thought to play identical roles in the DNA repair process.  However, this team of researchers recently showed that BCRA1 searches for any damaged DNA and then signals for help, while TopBP1 searches for DNA damaged specifically due to a problem with the DNA replication process and then signals for help.

Cancer Treatment Improvements?

When DNA becomes too damaged, cancer results.  The new cancer DNA can then copy itself and spread.  New ideas concerning radiation therapy making the cancer DNA unable to repair itself and unable to replicate are arising with this new discovery about the DNA-repairing proteins’ roles.  For instance, once cancer cells are damaged, proteins try to fix them, renewing the cancer cells.  Treatment could potentially be targeted at these proteins to stop them from fixing the cancer DNA and allowing the replication process to continue, now that we more fully understand their functions.

I find it fascinating to see how a rather basic discovery can have such major outcomes, and I am curious to see if further research will determine if certain medication can affect these powerful proteins.  Are there any other potential benefits to this protein-related discovery?

 

Original Article

For more information about DNA damage and repair and the role of the TopBP1 protein, click here. (Section 4 on this link talks about the similarities between BRCA1 and TopBP1.)

 

 

 

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