New research has found that before a cell divides into two new cells, it can spend several hours or even a day in a reversible intermediate state to ensure that it is ready for the process. This discovery sheds light on a fundamental aspect of biology, providing insights into the mechanisms and dynamics involved. This could have implications for the development of therapies for conditions such as cancer and other diseases.New research from Weill Cornell Medicine has uncovered a groundbreaking discovery about the intermediate state of cells, which can last for longer than a day and is reversible. This finding has important implications for developing future therapies for diseases, especially cancer. The study, published in Nature, describes how researchers were able to track the activation state of E2F, a protein that controls cell division, over time using new tools. The study revealed that E2F can remain in an intermediate state for an extended period, contrary to previous beliefs. This new understanding of cellular mechanisms could lead to innovative treatments for a variety of diseases.2F, prior to becoming fully activated, can enter a prolonged phase of partial and reversible activation. This phase may ultimately lead to full commitment to cell division or a return to the normal, non-dividing state known as “quiescence.” The exact role of this pre-commitment state in cell division is not yet fully understood, but it seems to function as a safety mechanism to prevent inappropriate cell division and may also trigger DNA-repair activities. This previously unknown aspect of cell biology has significant implications for understanding cancer, wound healing, and other processes related to cell division.”We believe that certain types of cancer cells may stay in an early stage before dividing in order to increase their chances of survival,” explained Dr. Tobias Meyer, the Joseph Hinsey Professor of Cell & Developmental Biology and a professor of biochemistry at Weill Cornell Medicine, who is the senior author of the study.
The study’s first author, Dr. Yumi Konagaya, who worked as a postdoctoral researcher in the Meyer Laboratory during the study, is now a principal investigator at Riken, a national research institute in Japan, and also a co-corresponding author with Dr. Meyer.
Cell division plays a fundamental role in the growth and development of living organisms.Cell division is a crucial process for the growth and repair of tissues in both embryos and adults. The activation of E2F signals the start of the division process, but it has always been a mystery how the cell avoids constant, inappropriate activations of E2F. Dr. Konagaya developed methods to track the detailed activation status of E2F in individual cells, providing insight into this process.The study focused on the E2F protein and its interactions with other signaling partners as cells transition from a resting state to the division process. The researcher discovered that E2F remains in a partially activated “primed” state, with some but not all of the necessary chemical modifications, called phosphorylations, having occurred. This primed state can last for more than a day before the cells either return to a resting state or proceed to cell division. This finding suggests that there is an intermediate stage between quiescence and cell division.The intermediate primed state gives cells the opportunity to process and combine the typical, fluctuating signals for cell division, helping to smooth out any “noise” and decreasing the likelihood of inappropriate division. However, the researchers believe that this state serves other purposes as well, such as aiding in DNA repair, as cells in this state display signs of activated DNA-repair processes. Dr. Meyer pointed out that a DNA-repair function could be beneficial for both cancer cells and healthy cells.
According to Dr. Meyer, ”Cancer cells often die when they divide due to the DNA damage they have accumulated, but this intermediate state activates DNA damage-repair mechanisms, so perhaps some cancers take advantage of this.”The scientists found that cells have an intermediate state before they divide, which allows them to repair themselves. They are now looking into how this pre-division state plays a role in cancer. By understanding the specific phosphorylation pattern of this state, they hope to create tests for detecting cancers in this stage, which could improve treatment options.