Biological Research Paper on Cancer Cells Awarded Carafoli Medal by BBRC

A 2025 paper on research led by Hyungjin Kim, a professor in the Renaissance School of Medicine Department of Pharmacological Sciences, has been awarded the prestigious Carafoli Medal by Biochemical and Biophysical Research Communications (BBRC).

BBRC is the premier international journal devoted to the very rapid dissemination of timely and significant experimental results in diverse fields of biological research.

The paper, "Loss of DNA replication fork protection by TIMELESS degradation supports oncogene-induced senescence," was identified by BBRC editors as having great potential for scientific impact.

"It provides important mechanistic insight into oncogene-induced senescence by demonstrating how TIMELESS degradation compromises replication fork protection and drives senescence-associated replication stress pathways," the board said in the award announcement. "After careful consideration, the Editorial Board selected your paper as the outstanding contribution among a highly competitive group of nominations. We believe your paper exemplifies the clarity, originality, and significance that the Carafoli Medal is intended to celebrate."

The Carafoli Medal recognizes the most impactful short communication published in BBRC over the past year. The award was established to highlight the importance of short-format contributions to the journal and to honour Professor Ernesto Carafoli, who served as a dedicated BBRC editor for over four decades.

Kim is the principal investigator who supervised the research project. Jennifer Park, a postdoc in Kim's lab and recent PhD graduate from Stony Brook, is the paper's leading author. Flaminia Talos, MD, associate professor in pathology and urology, collaborated with Kim and is a co-author.

When cells encounter a cancer-causing mutation, they engage an emergency brake mechanism called senescence, which forces cells into a permanent state of arrest, preventing them from developing into malignant tumors. It is well established that this brake is triggered when the cellular process to replicate the genome (i.e., DNA) breaks down and genotoxic stress accumulates. However, it was unclear whether this stress is just a secondary effect of the cancer cell proliferating too fast or the result of deliberate sabotage.

The research by Kim's team reveals that a common cancer-promoting gene, RAS, does not just strain cells with DNA damage by overworking them; in fact, it transmits a specific molecular signal to destroy a genome maintenance protein called TIMELESS (TIM) at the site of DNA replication.

Under normal conditions, TIM functions as a specialized protein that protects and stabilizes the DNA replication machinery. The study identified that when the RAS oncogene is activated, it triggers a series of reactions that break down the TIM protein. Without TIM, the DNA replication process stalls and collapses, which is the exact signal needed to switch off cell proliferation.

This study shows that our body has a programmed way to cripple the DNA replication process to stop cancer in its tracks in response to oncogene activation. Understanding how cells initiate this destruction signal and how some cancer cells learn to overcome this tumor-suppressive barrier could open new doors for therapies that exploit the unique DNA replication problems of cancer cells.