Cyclin Kinase-independent role of p21CDKN1A in the promotion of nascent DNA elongation in unstressed cells

Cancer develops when cells in the body mutate in ways that allow them to rapidly grow and divide. To protect cells from becoming cancerous, various molecules act like guardians to prevent cells from dividing when their DNA is damaged, or if they are short of energy. Other guardian molecules monitor the DNA copying process to ensure that the newly-made DNA is as identical as possible to the original DNA template. A protein called p21 belongs to the first group of guardian molecules: DNA damage triggers the production of p21, which prevents the cell from copying its DNA. This role relies on a section of the protein called the CDK binding domain. Cells that have already started to copy their genetic material also have low levels of p21. Mansilla et al. used human cells to investigate whether p21 is also involved in the process of copying DNA. The experiments show that the low levels of p21 act to increase the speed at which the DNA is copied. This activity helps to ensure that all of the cell’s DNA is copied within the time available, including sections of DNA that are harder to copy because they are more fragile and prone to damage. This newly identified role does not involve the CDK binding domain, but instead requires a different section of the p21 protein known as the PCNA interacting region. Mansilla et al. propose that p21 plays a dual role in protecting us from developing cancer. The PCNA interacting region is also found in other proteins that are involved in copying DNA. Therefore, a future challenge is to find out how these proteins interact with each other to ensure that cells accurately copy their DNA in a timely fashion.