Graphical abstract
Scientists find cancer weak spot in backup DNA repair system | Scripps Research
Scientists at the Scripps Institute have discovered a defective DNA repair mechanism that would normally trigger cell death but which, paradoxically, keeps cancer cells alive. They have recently published their findings, open access, in Cell Reports. It is exactly the sort of biochemical complexity that creationists routinely mistake for evidence of intelligent design, having been led to believe that well-designed systems must be highly complex. In reality, good intelligent design is minimally complex: complexity increases the risk of failure, is harder to maintain, and is more energetically costly.
The DNA “code” is one of creationism’s favourite props for its familiar ignorance-plus-incredulity-therefore-God-did-it argument — a textbook god-of-the-gaps false dichotomy. Yet even a superficial look beneath the metaphor reveals that DNA replication and repair are very far from the flawless perfection we would expect from an omniscient, omnipotent and omnibenevolent deity — especially when it comes to its supposedly special creation, humankind. What we actually observe is a fragile, error-prone system patched together by evolutionary history rather than foresight.
The system is only needed in the first place because cell replication in multicellular organisms remains essentially identical to that of single-celled organisms. Despite the fact that the benefits of multicellularity arise from cell specialisation into tissues and organs with discrete functions — each requiring only a tiny fraction of the genome — every cell is forced to copy the entire DNA complement every time it divides. This vast waste of energy and resources serves only to multiply the probability of error, and errors are not rare anomalies but routine occurrences. This is not the signature of intelligent design.
The Scripps Institute team have shown that some cancer cells survive precisely because the normal high-fidelity repair system fails. When that happens, a crude backup mechanism takes over — an emergency repair process that is little more than a biological kludge and which introduces further errors as it works. It is rather like calling out an emergency plumber who fixes one leak by installing a long section of pipe riddled with smaller leaks. Would anyone describe that as intelligent workmanship?
Specifically, cancer cells with a faulty senataxin (SETX) protein — which normally helps untangle problematic RNA–DNA structures known as R-loops — accumulate these tangles at sites of DNA damage. The resulting chaos prevents the cell’s accurate repair machinery from operating properly, leaving exposed DNA strands. In response, the cell switches to an emergency process called break-induced replication (BIR). This allows the cell to survive by rapidly copying large stretches of DNA, but at the cost of introducing numerous additional errors.
Ironically, this desperate workaround creates a fatal dependency. SETX-deficient cancer cells rely on BIR and its associated proteins to stay alive, and if that pathway is blocked they can no longer repair their DNA and die. This vulnerability may provide a route to targeted cancer therapies — and at the same time offers yet another example of how biological reality stubbornly refuses to conform to creationist fantasies of perfect, intelligently designed systems.
Cell repair and why it fails. Background: How Cells Normally Repair Broken DNAThe Scripps team’s work is explained in a Scripps Institute news release.
Every time a cell divides, its DNA must be copied with extreme accuracy. To manage the inevitable mistakes, cells rely on several repair systems. The most accurate of these fix DNA breaks by using an intact copy of the DNA as a template, ensuring minimal errors. These systems evolved to keep cells alive long enough to reproduce — not to produce perfection.
When these high-fidelity repair mechanisms fail, cells may activate backup pathways that prioritise survival over accuracy. These emergency systems are faster but far more error-prone, increasing mutation rates and genomic instability.
What Are R-Loops and Why Are They a Problem?
R-loops form when newly made RNA sticks back onto its DNA template, creating tangled RNA–DNA hybrids. While small numbers of R-loops are normal, excessive accumulation interferes with DNA replication and repair.
Cells use specialised proteins, such as senataxin (SETX), to unwind these structures. When this process fails, DNA damage accumulates — a major driver of mutation, cancer, and cell death.
Break-Induced Replication (BIR): A Last-Resort Repair System
Break-induced replication is a DNA repair pathway normally used only in emergencies, such as when a chromosome breaks and no matching template is available. Instead of repairing a small region, BIR copies large sections of DNA in one sweep.
This makes it effective at keeping damaged cells alive, but at a heavy cost: it frequently introduces errors, rearranges chromosomes, and increases mutation rates. In cancer cells, this “survival at any cost” strategy helps tumours persist and evolve resistance to treatment.
Why Cancer Exploits Faulty DNA Repair
Cancer cells are not well designed — they are barely functional survivors. Many cancers thrive because they disable normal error-checking systems and rely on unstable repair pathways that allow rapid genetic change.
This instability fuels tumour growth and drug resistance, but it also creates weaknesses. Cancer cells that depend on emergency repair mechanisms can be selectively killed by blocking those pathways, leaving healthy cells largely unaffected.
Evolution, Not Design
DNA repair systems were not engineered from scratch. They are modified versions of ancient mechanisms that evolved in single-celled organisms, long before multicellular life existed.
Natural selection favours systems that are “good enough” to reproduce — not systems that are optimal, efficient, or elegant. The patchwork nature of DNA repair is exactly what evolutionary theory predicts, and exactly what intelligent design cannot explain.
Scientists find cancer weak spot in backup DNA repair system
New findings from Scripps Research reveal how certain tumors survive DNA damage—and point to a strategy for targeting them.
The DNA inside our cells is constantly being damaged, and one of the worst kinds of damage is a double-strand break—when both sides of the DNA helix are cut at once. Healthy cells can normally fix these breaks using highly precise repair systems, but when those systems fail, cells sometimes resort to a less accurate backup method. Now, scientists at Scripps Research have discovered when and how this backup repair pathway gets activated, and how the process could be turned against cancer cells that rely on it to survive.
The study, published in Cell Reports on October 28, 2025, focused on a protein that unwinds twisted strands of genetic material, including RNA-DNA tangles called R-loops. These temporary, harmful “knots” form when newly made RNA sticks to its DNA template instead of detaching, leaving one DNA strand exposed.
R-loops are important for many different cell functions, but they must be tightly controlled. If they aren’t properly regulated, they can accumulate to harmful levels and cause genome instability.
Professor Xiaohua Wu, senior author
Department of Molecular and Cell Biology
The Scripps Research Institute
La Jolla, CA, USA.
The study zeroed in on a type of helicase protein—a class of molecular motors that unwind genetic tangles—called senataxin (SETX). SETX mutations are known for their role in rare neurological disorders, including ataxia and a form of amyotrophic lateral sclerosis (ALS). SETX mutations are also found in some types of uterine, skin and breast cancers. This raises the question of how tumor cells manage to survive the stress caused by excessive R-loops.
To investigate, Wu’s team used SETX-deficient cells with high levels of R-loops and tracked how they responded when double-strand breaks occurred at the sites of R-loops. As expected, these cells showed a surge in DNA damage, but they also switched into a frantic repair overdrive.
We were surprised but excited to find that the cell turns on an emergency DNA repair mechanism called break-induced replication (BIR).
Professor Xiaohua Wu.
This BIR mechanism normally rescues damaged DNA forks during replication, but it can also act as a backup system for double-strand breaks. The process involves proteins that rapidly copy large sections of DNA to patch up broken strands—unlike the smaller, more precise fixes of the usual repair pathway. But because BIR copies the DNA so extensively and quickly, it often introduces errors.
It’s like an emergency repair team that works intensively but makes more mistakes.
Professor Xiaohua Wu.
The researchers found that when SETX is missing, R-loops build up at the break sites, scrambling the cell’s normal repair signals. The broken DNA ends are trimmed too far, exposing long stretches of single-stranded DNA, which in turn attracts the BIR machinery including PIF1, an essential helicase for the BIR process. The combination of exposed DNA strands and PIF1 kick-starts BIR for damage repair.
Despite its error-prone nature, BIR can keep SETX-deficient cells alive, but it also creates a critical weakness. The cells become dependent on BIR for survival, meaning that if BIR is blocked, the cells have no way to repair the breaks, and they die. This concept, known as synthetic lethality, is the basis of several modern targeted cancer therapies.
Wu’s team found that SETX-deficient cells rely heavily on three BIR-related proteins: PIF1, RAD52 and XPF.
What’s important is that these aren’t essential in normal cells, which means we could selectively kill SETX-deficient tumors.
Professor Xiaohua Wu.
The findings are promising, but Wu notes that translating them into treatment will take time.
We’re now exploring ways to inhibit these BIR factors, trying to find ones with the right activity and low toxicity.
Professor Xiaohua Wu.
Her lab is also studying which types of tumors accumulate the highest levels of R-loops and under what conditions. Identifying the best cancer candidates for BIR-targeted therapy will be an important next step.
Although SETX deficiency isn’t the most common cancer mutation, many tumors accumulate R-loops through other mechanisms, such as oncogene activation or hormone signaling like estrogen in certain breast cancers. That means the therapeutic opportunities could apply to a broader set of cancers, not just those with SETX mutations.
In addition to Wu, authors of the study “Break-induced replication is activated to repair R-loop-associated double-strand breaks in SETX-deficient cells” include Tong Wu, Youhang Li, Yuqin Zhao and Sameer Bikram Shah of Scripps Research; and Linda Z. Shi of the University of California San Diego.
Publication:
Within the internal logic of Intelligent Design creationism, there is no coherent way to avoid the conclusion that cancer itself must be designed. If DNA repair systems, their failure modes, and the emergency pathways that take over when they fail are all the product of deliberate intent, then so too are the mechanisms that allow cancer cells to survive, adapt, and ultimately kill their host. One cannot credit an intelligent designer with the system while blaming “the Fall”, entropy, or corruption for its outcomes, because the outcomes follow directly and predictably from how the system works.
The Scripps Institute findings make this particularly stark. Cancer cells do not survive by accident or by some mysterious external interference; they survive because the genome contains built-in backup mechanisms that prioritise survival over accuracy, even when that survival is catastrophically harmful at the level of the organism. A designer who implemented such systems knowingly would have designed not merely the possibility of cancer, but its persistence, evolvability, and resistance to treatment. That is not an unfortunate side effect — it is a functional feature.
Evolution, by contrast, predicts exactly what we observe. DNA repair pathways are inherited, modified versions of ancient survival mechanisms that evolved in single-celled organisms, where keeping a damaged cell alive long enough to reproduce is the only criterion for success. In multicellular organisms, those same mechanisms become dangerous liabilities, but natural selection has no foresight and no capacity to redesign from scratch. What we see in cancer is not evidence of malign intent or poor craftsmanship, but the unavoidable consequence of descent with modification.
Intelligent Design creationism therefore faces a choice. It can accept that cancer is, in a meaningful sense, designed to survive and kill — or it can abandon the claim that biological systems are the product of intelligent foresight. Evolution requires no such contortions. The messy, error-prone, stop-gap nature of DNA repair is not an embarrassment to evolutionary theory; it is precisely what it predicts.
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