March 10, 2026 | Austin, Minn. — Understanding the nuances of how or why a particular cancer treatment works in a certain context helps researchers develop new, effective treatment strategies and improve existing ones. This is the line of thinking that led researchers at The Hormel Institute, University of Minnesota, to investigate how cancer cells respond to treatment with hydroxyurea, a commonly used chemotherapy drug. Their exploration yielded new insights on the DNA replication process that could be useful for further enhancing patient treatments and improving cancer outcomes.
Authors of the study include Researcher 5 Srinivasu Karri, PhD, and Assistant Professor Chuanhe Yu, PhD. Their recent review is published in the scientific journal DNA.
“Cancer cells already operate under high stress,” Dr. Karri explained. “Understanding how therapies exploit this weakness can help design better, safer, and more precise treatments for patients.”
During DNA replication, a cell makes an identical copy of its DNA before it divides to create two new cells. This gives the new cell its own full genome, or instructions, that it will use to carry out essential processes.
During the DNA replication process, that “double helix” shape of DNA you might have heard about in science class unravels into two separate DNA strands. As the DNA strands separate from the double helix, the shape becomes a Y-shaped “fork” structure. This structure that forms during the DNA replication process is referred to as the “replication fork.”
Hydroxyurea is a chemotherapy drug used to treat certain cancers, such as melanoma and chronic myelogenous leukemia, as well as blood diseases, like sickle cell anemia. Hydroxyurea’s ability to suppress DNA replication also makes it a key tool for research that studies DNA replication stress, genome instability, and more.
In their review, the Yu Lab reviewed the DNA replication process and the impact hydroxyurea has on DNA replication forks to better understand the mechanisms at play and how they could be used for possible therapeutic benefits.
“We show that hydroxyurea does more than simply block DNA building blocks — it also increases oxidative stress and disrupts key metal-dependent proteins needed for DNA replication. Together, these effects reshape how cancer cells copy their DNA and respond to treatment,” Dr. Karri said.
Key findings from the study include:
- Hydroxyurea triggers a complex stress response that involves factors such as oxidative damage, the disruption of metal-dependent proteins important for replication, and activation of the replication checkpoint.
- The above stress responses during replication affect the two DNA strands differently, revealing an unexpected asymmetry in how cells manage replication stress. This challenges the traditional view of the replication fork as a symmetrical unit.
- Distinct regulatory mechanisms for leading- and lagging-strand machinery during replication are connected to certain checkpoint signaling responses triggered by hydroxyurea.
- Replication checkpoint pathways may remodel the architecture of replisomes (which help to replicate DNA at the replication fork) in response to oxidative stress, providing new insight into how forks adapt to remain stable.
“These insights explain why hydroxyurea is effective against cancer cells and suggest new strategies to improve cancer therapies. By targeting oxidative stress, metal cofactor metabolism, and checkpoint signaling together, future treatments may become more effective and selective,” Dr. Karri said.
“We hope these findings will stimulate further research into metal cofactor biology, replisome remodeling, and checkpoint regulation, and inspire new approaches to precision cancer therapy,” Dr. Karri added.
You can read the paper here: https://doi.org/10.3390/dna6010009
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ABOUT THE HORMEL INSTITUTE
Founded in 1942 by Jay C. Hormel and The Hormel Foundation, The Hormel Institute, University of Minnesota, makes scientific advancements that enhance wellbeing and extend human life. For more than 80 years, we have pursued our mission to conduct research and provide education in the biological sciences with applications in medicine and agriculture. A part of the University of Minnesota's Research and Innovation Office, The Hormel Institute partners with the region's leading biomedical research facilities, including Mayo Clinic.