23. Genes are fragile. A variety of things can damage them, including sunlight and how cells copy them.
My Initial Reaction
Since my genetics class is dealing with DNA replication now, and will next turn our attention to the topic of mutations, this is a prime time to have students check this Fact!
I (wrongly) guessed that, once again, discussion about biology would get mired in semantics. For example, I envisioned receiving many comments from students about whether it is "genes" that are fragile or DNA that is fragile? A gene is a part of a chromosome, so it is composed of DNA - and genes are, generally speaking, no more or less fragile than non-gene regions of chromosomes.
Student Responses
To my surprise, then, students quickly identified many different sources to support the Fact. Many citations were to review papers, not primary research literature. But, if you like, you can follow the references in the reviews to get at the published data.
Representative responses include the following pair:
“Genes become 'damaged' quite often--often enough that there are regulators whose main function are to fix these damaged DNA.”
“There’s some regions in DNA synthesis that may display certain breaks or constrictions that can lead genes to be fragile.”
Many students identified manuscripts, like the review by Rastogi et al. (2010), that only begin to survey the trove of data we have on how ultraviolet light from the sun can damage DNA and cause mutations.
Some, related to the second quote, noted that DNA is not only prone to damage by light, and by chemicals, but also by our own cellular processes, even those that are meant to accurately replicate our DNA when our cells divide so that the two daughter cells resulting from cell division each have a copy of each chromosome. As Ma et al. (2012) review, there are number of so-called "fragile sites" on our chromosomes, that are (relatively) frequently observed to break during cell division. Some of these chromosome breakage events happen when the failsafe mechanisms in our cells don't work properly and allow cell division to begin before our chromosomes are finished replicating.
I was also quite impressed by other students, who (as in the first quote) identified that the presence of DNA repair machinery in our cells is proof itself that DNA is fragile, such that our cells have evolved tools (in the form of enzymes) to seek out and repair mutations and chromosomal breaks. As we'll see shortly, some of these processes aren't perfect.
Related to DNA repair, I'll add a new Fact to the existing 100: most humans have the breast cancer predisposition gene BRCA1. I even have it. You know why? Because this gene encodes a protein that is a DNA repair enzyme. The reason it is known as a breast cancer gene is because mutation of this gene (that is: loss of its normal, protective function) makes people more likely (predisposed) to develop breast cancer because their cells are less able to repair DNA damage. Thus, it is only particular (mutant) versions of this gene that are more likely to lead to breast cancer. When people are genetically tested for breast cancer susceptibility, one of the targets of testing is to check the BRCA1 gene for such mutations. Actor Angeline Jolie famously elected to have a prophylactic double mastectomy after she learned that she had such a mutation.
Student Decision: Fact or Fiction?
This one was overwhelmingly fact.
Literature Cited
- Ma et al. (2012) "Common Fragile Sites: Genomic Hotspots of DNA Damage and Carcinogenesis" Int J Mol Sci 13:11974-11999.
- Rastogi et al. (2010) "Molecular Mechanisms of Ultraviolet Radiation-Induced DNA Damage and Repair" J Nuc Acid 592980.
