4 July 2024 Thesis defense Clément Rouillon ‘One Chaperone to Rule Them All: Deciphering How Chromatin is Assembled During DNA Replication’ Back to news On July 4th Clément Rouillon defended his thesis ‘One Chaperone to Rule Them All: Deciphering How Chromatin is Assembled During DNA Replication’. He did his PhD in the Mattiroli group where he investigated the role of histone chaperones during chromatin and DNA replication in cell proliferation. He specifically focused on the CAF-1 histone chaperone which is critical for chromatin assembly during DNA replication. Given the importance of CAF-1 in cell division, it is often overexpressed in cancer as then cell proliferation is uncontrolled. Rouillon’s work can pave the way for the development of tools that could enable the use of CAF-1 as a routine biomarker in cancer diagnosis and potentially as a therapeutic target. Our bodies are made up of trillions of cells, most of which have a limited lifespan and must reproduce to replace the old ones. This reproduction process is referred to as cell division. During this process the cells need to copy its DNA in order to pass it on to the daughter cells. When a cell copies its DNA, it’s not just about making an exact duplicate of the genetic code. The newly synthesized DNA also needs to be properly packaged into chromatin, a complex structure made of DNA and proteins called histones that together, form chromosomes. This packaging process involves many different proteins, including specialized ones known as histone chaperones. Chromatin stores genetic and epigenetic information, which ensures that cells keep their identity during cell division. Therefore, in order to ensure that a dividing cell receives all the correct information, both the DNA and the chromatin organization will be copied. Histones package DNA There are many proteins involved in copying DNA and chromatin, including the specialized histone chaperones. During Rouillon’s PhD, he researched one specific histone chaperone, namely the Chromatin Assembly Factor 1 (CAF-1). This chaperone helps place DNA-packaging proteins called histones onto the new DNA so that it can be organized into chromatin. CAF-1 is guided to the right spot by another protein called Proliferating Cell Nuclear Antigen (PCNA), which helps coordinate a multitude of DNA related processes. During his PhD, Rouillon researched the interaction between PCNA and CAF-1 during chromatin replication. An interaction to investigate Through multidisciplinary approaches such as genomic-based assays, biochemical reconstitutions and structure predictions, Rouillon’s research showed that the interaction between PCNA and CAF-1 is crucial for properly assembling chromatin during DNA replication. Their work has improved understanding of the structural details of how CAF-1 and PCNA interact. Understanding these interactions better could help improve our knowledge of cell processes and potentially lead to advancements in cancer diagnosis and treatment. Clément Rouillon now works as a postdoc in Benjamin Rowland’s group at the NKI in Amsterdam.
