Scientists reveal how cells “back up” DNA replication to survive severe damage

DNA helicase HELQ promotes replication fork reversal, protecting cells from toxic DNA crosslinks

Institute for Basic Science

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A representative figure showing that HELQ-deficient cells fail to undergo normal fork slowing after MMC (a crosslinking agent) treatment, consistent with defective fork reversal.

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Credit: Institute for Basic Science

Every time a cell divides, it must copy its DNA with extraordinary precision. But this process is constantly challenged by DNA damage. Among the most dangerous lesions are DNA interstrand crosslinks (ICLs), which chemically bind the two strands of DNA together and block the machinery responsible for copying the genome. These lesions are not only produced naturally in cells but are also deliberately induced by widely used chemotherapy drugs such as cisplatin and mitomycin C. If not properly managed, they can cause catastrophic DNA breakage and cell death.

A research team led by Dr. Kei-ichi TAKATA at the Center for Genomic Integrity within the Institute for Basic Science (IBS) has uncovered how cells protect themselves from this severe form of DNA damage. Their findings reveal that the DNA helicase HELQ plays a key role in stabilizing stalled DNA replication by actively remodeling DNA structures.

When DNA is being copied, it forms a Y-shaped structure known as a replication fork. If the fork encounters an obstacle such as a crosslink, it can stall abruptly. Without proper handling, this can lead to mutations, chromosome breakage, or cell death. The researchers found that HELQ enables a protective response called replication fork reversal. In this process, the replication machinery temporarily “backs up,” converting the fork into a four-way DNA structure. This stabilizes the damaged site and gives the cell time to repair the DNA safely.

Using DNA fiber analysis, the team observed that normal cells slow down replication when exposed to crosslinking agents—a hallmark of fork reversal. In contrast, cells lacking HELQ failed to show this response, indicating that HELQ is required for this protective slowdown. To directly visualize these structures, the researchers used electron microscopy and confirmed that HELQ-deficient cells form significantly fewer reversed forks under replication stress.

The study further shows that HELQ is not just a passive participant but an active molecular motor. Further experiments showed that HELQ acts directly at damaged replication sites, using its enzymatic activity to reshape DNA and promote fork reversal. This function depends on HELQ’s enzymatic activity—when the researchers tested a helicase-inactive mutant, cells lost the ability to properly slow replication under DNA damage, confirming that HELQ’s activity is essential. HELQ was also found to work together with the BCDX2 complex, a DNA repair complex, with both acting in the same pathway to promote fork reversal.

Previous studies had shown that cells lacking HELQ are unusually sensitive to DNA crosslinking agents, but the reason was unclear. This study now provides a clear explanation: without HELQ, cells cannot properly reverse and stabilize stalled replication forks. As a result, DNA damage accumulates and becomes more toxic. The researchers also found that HELQ helps limit error-prone repair pathways. In its absence, cells rely more heavily on alternative mechanisms that can introduce mutations, highlighting HELQ’s role in maintaining genome stability.

Because DNA crosslinking agents are widely used in cancer treatment, these findings have important implications for cancer biology. Differences in HELQ activity may influence how cancer cells respond to chemotherapy, potentially affecting both sensitivity and resistance to treatment. “This study explains why HELQ-deficient cells are highly sensitive to DNA crosslinking agents,” said Director MYUNG Kyungjae. “By showing that HELQ directly promotes replication fork reversal, we now have a clearer picture of how cells protect their genomes against one of the most toxic forms of DNA damage.”

Overall, the study identifies HELQ as a critical regulator of replication fork remodeling. By enabling stalled replication forks to reverse and stabilize, HELQ helps cells survive severe DNA damage while minimizing mutations. These findings advance our understanding of how human cells maintain genome integrity under replication stress and provide a foundation for future studies on how cancer cells respond to DNA-damaging therapies.

The study was published in Nucleic Acids Research on April 29, 2026.

 

A schematic model proposing that HELQ acts at an RPA-coated leading-strand gap to drive replication fork reversal and facilitate safe interstrand crosslink repair.

Credit

Institute for Basic Science

Journal

Nucleic Acids Research

DOI

10.1093/nar/gkag332 

Method of Research

Experimental study

Subject of Research

Cells

Article Title

The DNA helicase HELQ promotes replication fork reversal in coordination with BRCA2- and FANCD2-mediated repair pathways

 

The merits and pitfalls of metaphor use in science communication

Metaphors often use imagery and comparison as a bridge to simplifying ideas and getting a point across. They are especially useful in science communication, but they often come equipped with faults

Ocean-Land-Atmosphere Research (OLAR)

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Illustration of key metaphors used in climate science, including the “ocean conveyor belt” and “tipping points,” alongside models and data. The figure highlights how metaphors provide intuitive understanding of complex Earth system processes but must be interpreted in the context of models, observations, and uncertainty.

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Credit: Gerrit Lohmann (AWI / University of Bremen)

Effective science communication is a powerful but underrated tool. Metaphors, a common literary device, draw connections between unlike things and are often conceptually, innately understood. In science and science communication, these figures of speech act as a means of structuring concepts to provide the basis for further exploration. The use of metaphors in science can be a catalyst for change, invention, and, unfortunately, misunderstanding. Metaphors should be used responsibly when attempting to make complex scientific concepts easily understandable, and should weigh the accuracy and accessibility of information in a favorable balance.

 

Dr. Gerrit Lohmann published his research in Ocean-Land-Atmosphere Research in March 2026.

 

In this research, two popular metaphors for describing climate-related issues were explored: the “ocean conveyor belt” metaphor and the “tipping point” metaphor.

 

Both of these metaphors began as concepts with scientific origins and evidence to create the framework for the literary decor. The metaphor of the ocean conveyor belt started as a means to describe the overturning circulation driven by deep water formation from the North Atlantic Ocean on a global scale. This metaphor helped propel hypotheses in the scientific community and also fostered more interdisciplinary communications; however, the oversimplification of the metaphor neglected important facets of its origins. The three-dimensional structure of oceanic circulation and the slew of other dynamics in the globe’s oceans are difficult to wrap succinctly in one metaphor, and to many, the conveyor belt imagery stuck around, but true understanding never arrived.

 

Similarly, the “tipping point” metaphor resonated strongly across disciplines and with the public. This metaphor communicates the possibility of abrupt change and, though it provided major motivation for further experiments, policy change and the public’s attention, it also became a focal point for fatalists and sensationalists. “Tipping elements,” individual issues with a threshold and consequence when surpassed, were later introduced as a way to further the metaphor.

 

For example, a tipping point often cited is a global temperature increase of 1.5°C leading to the irreversible damage and downfall of many of Earth’s systems, sending us into a catastrophe amounting to the end of days as we know it. However, this way of framing can be misleading to those with no basis of understanding climate science, leading to thoughts of instantaneous disaster versus gradual shifts that would take lifetimes to fully experience.   

 

“Both the conveyor belt and tipping point metaphors illustrate how science progresses through dialogue between models, data, and conceptual simplifications,” said Gerrit Lohmann, professor of climate physics and author of the study.

 

Metaphors, like the tipping point, can oversimplify to the point of being problematic. The binary framing of this metaphor with the image of imaginary thresholds being crossed with sudden, dramatic, dire implications is not entirely the truth, and like most things, the truth is somewhere in between the extremes.

 

Improving metaphors by balancing accuracy and accessibility is not as easy as it seems, given the amount of nuance involved in nearly every subject, especially within the sciences.

 

Lohmann suggests integrating communication research with practical evidence and models to remove some of the fog that can surround metaphors heard or seen without a base of knowledge to check against. When metaphors dramatize risk, Lohmann also suggests adding a clear explanation along with it to reduce negative feelings such as fear and vulnerability to the information being depicted. The better the metaphor, the more likely it is that better scientific practices and policies can be put into place to create actionable and measurable change.

 

Gerrit Lohmann of the Alfred Wegener Institute and the Univeristy of Bremen is the researcher and author of this study.

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Journal

Ocean-Land-Atmosphere Research

DOI

10.34133/olar.0140 

Method of Research

Commentary/editorial

Subject of Research

Not applicable

Article Title

Models and Metaphors for Interdisciplinarity and Communication in Earth System Science

 

New national study published in The Permanente Journal shows physicians are changing their reasons for leaving clinical practice early

American Medical Association researchers found burnout, chronic workplace stress, administrative burden, and unrealistic patient expectations are now among the top reasons physicians leave clinical practice early

The Permanente Federation

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OAKLAND, Calif., May 7, 2026 -- A study published today in The Permanente Journal sheds light on what’s driving physicians to leave clinical practice early — and how those reasons are shifting. Researchers from the American Medical Association (AMA) analyzed survey responses from 971 clinically inactive physicians across all specialties who completed residency between 2000 and 2022. Their findings offer insights into why physicians are stepping away from patient care — or not entering the clinical workforce at all — especially as the nation faces a growing physician shortage.

“We hope that by better understanding what drove these physicians away from the clinical practice of medicine, we might uncover meaningful insights that will help us improve physician professional satisfaction and retention,” said Sea Chen, MD, PhD, the paper’s corresponding author. Chen works for the AMA in Chicago. The paper, “Why Have All the Doctors Gone? Insights Into Early Clinical Departure Among U.S. Physicians: A National Survey,” is the only study of its kind to be published in the United States in well over a decade. It is available open access.

Seeking to ascertain reasons for the “enlarging leak in the pool” of clinically practicing clinicians, the investigators found that a “somewhat surprising proportion” of participants were fully residency-trained physicians who never entered the clinical workforce. The researchers suggest that additional studies are needed to understand why.

Of those who entered clinical practice, the researchers identified a shift in motives among those who left the profession compared with earlier findings. Data from 2008 show that early departure was more likely to be due to personal health issues, rising malpractice insurance premiums, perception of hassle, and lack of professional satisfaction. Updated findings show that rationale focuses more on burnout, chronic workplace stress, administrative burden, and unrealistic patient expectations.

As Americans feel the strain of ongoing and anticipated physician shortages, the AMA research is timely, pointing to a need for hospital systems to bolster retention strategies.

“As the health care system works to further expand the physician pipeline by opening new medical schools and adding more residency slots, it’s worth asking whether we should also focus on supporting physicians who are already trained,” Chen said.

The researchers also evaluated gender disparities in physician decisions to exit clinical practice.

“The women in our study left clinical practice earlier than men, and they left due to pressures like caring for young children or other family members more often than men,” Dr. Chen said. “Addressing these issues — through better childcare access, flexible work policies, and equitable treatment — could help retain more women in the physician workforce.”

About The Permanente Journal

The Permanente Journal, published by The Permanente Federation, is a premier publication for content related to health care delivery science, value-based and high-value care, and clinical and applied research. A diamond open-access publication, The Permanente Journal has been publishing research on the practices of high-quality, evidence-based, equitable, and value-based and high value care since 1997.

 

About The Permanente Federation

The Permanente Federation is the national leadership and consulting organization of Permanente Medical Groups, which provide high-quality, affordable health care to the members of Kaiser Permanente. The Federation works to spread the ethical and compassionate value-based care we call Permanente Medicine. Our model of care is physician-led, patient-centered, and team-delivered. We foster and accelerate medical research, clinical innovation, and performance improvements. With Kaiser Foundation Health Plans and Kaiser Foundation Hospitals, we’re expanding the reach of Kaiser Permanente’s unique approach to integrated care delivery, transforming health care in America. Find out more at permanente.org.

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Journal

The Permanente Journal

DOI

10.7812/TPP/25.219 

Method of Research

Data/statistical analysis

Subject of Research

People

Article Title

Why Have All the Doctors Gone? Insights Into Early Clinical Departure Among U.S. Physicians: A National Survey

Article Publication Date

7-May-2026

Brexit did not just shake Britain - it sent financial shockwaves across Europe

Brexit sent waves of financial volatility through European markets, reshaping how risk travelled between countries and exposing how tightly connected the continent’s financial systems had become, according to new research from the University of Surrey

University of Surrey

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Brexit sent waves of financial volatility through European markets, reshaping how risk travelled between countries and exposing how tightly connected the continent’s financial systems had become, according to new research from the University of Surrey. 

Analysing more than two decades of stock market data across the EU, Surrey researchers found that Brexit-related events significantly increased volatility spillovers between European markets. Political announcements, negotiations and leadership changes during the Brexit process repeatedly triggered financial reactions that spread across the EU and markets.  

The team argue that rather than being a single economic shock, Brexit functioned as a prolonged sequence of uncertainty. Each political milestone, from the referendum result to parliamentary votes and trade negotiations, altered investor expectations and sent signals through financial markets across Europe. 

The analysis shows that large financial markets tend to transmit volatility to smaller ones. France emerged as the most persistent transmitter of volatility across the EU during the Brexit period, while the UK acted as a major transmitter during the early stages of negotiations. Smaller markets, including Ireland, Portugal and Spain were among those most affected by the turbulence.  

To understand how these shocks travelled through the system, the Surrey team examined daily market data from EU countries between 2000 and 2021. They combined advanced volatility modelling with a new “Brexit intensity” index that tracked around 500 political and economic events during the Brexit process. Each event was weighted based on how strongly financial markets reacted, using indicators including stock returns, exchange rate movements and market volatility measures.  

Dr Vasileios Pappas, lead author of the study and Associate Professor in Accounting and Finance at the University of Surrey, said: 

“Brexit was a long series of political shocks that financial markets here in the UK and across the continent had to absorb in real time. What we show is that each major announcement or political shift sent signals through European markets, spreading uncertainty far beyond the UK.” 

The findings also found that Brexit weakened financial integration within Europe. Following the 2016 referendum, the level of volatility transmission between EU markets dropped sharply, suggesting that markets began reacting more independently as political uncertainty grew. 

Dr Pappas added: 

“Financial markets are closely linked across borders. When uncertainty rises in one country it rarely stays there. By understanding how these shocks travel we can better anticipate the risks and strengthen financial stability.” 

 

[ENDS] 

• Dr Vasileios Pappas is available for interview. Please contact: mediarelations@surrey.ac.uk to arrange.  

• The full study has been published in the International Journal of Finance & Economics. 

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Journal

International Journal of Finance & Economics

Article Title

Brexit and Its Impact on EU Financial Markets

 

Planning for hydrogen under geopolitical uncertainty

Research Institute for Sustainability (RIFS) – Helmholtz Centre Potsdam

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Scenarios for renewable-hydrogen-based industrial production

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Credit: RIFS Potsdam Source: L. Eicke et al. (2026)

Many hydrogen strategies for energy-intensive industries do not adequately address geopolitical risks. Instead, they often assume stable trading relationships and reliable alliances – assumptions which are increasingly questionable in light of recent conflicts and sanctions. Policymakers and businesses should therefore give greater consideration to alternative future scenarios. This is the key finding of a new study published in Nature Reviews Clean Technology.

Energy-intensive industries such as the steel and chemical sectors are under pressure to drastically reduce their CO2 emissions and are increasingly turning to green hydrogen. This raises a strategically important question: Will this also lead to shifts in global supply chains? Will energy-intensive production move to locations where renewable hydrogen can be produced cheaply – or will it remain in today’s industrial centres, which will then import hydrogen?” explains lead author Laima Eicke from the Institute for Sustainability (RIFS) at GFZ. The researchers investigated how key factors with high levels of uncertainty – including transport infrastructure, investment conditions, and industrial policy – interact under different geopolitical conditions. The study analyses three possible scenarios and their implications for the environment and global equity.

The Fuel Switch scenario is currently the most widely discussed in Europe and underpins many national hydrogen strategies. In this scenario, infrastructure in existing industrial centres is converted to operate on hydrogen, which, to an extent, would need to be imported, altering global industrial geography only slightly. However, the success of these strategies will depends to a large degree on the construction of extensive transport infrastructure, stable trading relationships, and limited efforts by hydrogen producing countries to develop their industrial value chains.

The latter seems unlikely: significant differences in the cost of hydrogen production around the world, and growing industrial policy ambitions in resource-rich countries, could redirect investment and production towards these countries to a greater extent than previously assumed. Relying exclusively on this scenario risks misdirected investment in infrastructure that would ultimately prove unsuitable.

In the Industrial Relocation scenario, energy-intensive industries shift production capacities to locations where renewable energy is abundant and inexpensive, often in low- and middle-income countries. Transport distances, costs, and emissions would fall, and these countries could see opportunities for industrial development. Established industrial regions would face new challenges in managing the social impact of economic restructuring. The study also shows that many countries in the Global South would still likely require external partnerships and support to realise these opportunities.

The hybrid Dispersed Production scenario offers a middle ground in which hydrogen is produced and processed on-site into intermediates such as ammonia or directly reduced iron, which are then transported to existing industrial centres for use in the manufacturing of end products such as steel. The study shows that this scenario can deliver many of the cost benefits of relocating production while also spreading value creation across more regions. This could make it attractive to both producing and importing countries.

The authors conclude that hydrogen and industrial strategies should explicitly consider alternative geopolitical futures, rather than tacitly assuming the continued existence of stable alliances and liberal trading conditions. For economies reliant on imports, this means weighing which industries should be strategically supported and making infrastructure decisions that will remain viable under different scenarios. For resource-rich countries in the Global South, it means creating suitable policy and regulatory environments, coupled with regional cooperation, to ensure they actually benefit from the transition.

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Journal

Nature Reviews Clean Technology

DOI

10.1038/s44359-026-00164-3 

Method of Research

Systematic review

Subject of Research

Not applicable

Article Title

Geoeconomic scenarios of renewable-hydrogen-based industrial production