Sara Buonomo

Investigating the temporal dynamics of DNA replication and its role in epigenetic inheritance.

Sara Buonomo is the Chair of chromatin replication and architecture at the Institute of Cell Biology, School of Biological Sciences. Her research focuses on the molecular mechanisms coordinating DNA replication, transcription and epigenetic inheritance. Employing uses a range of model systems, primarily transgenic embryonic stem cells manipulated via Cas9/CRISPR, her research integrates genomics, bioinformatics, cell biology and imaging approaches.

Sara completed her undergraduate studies in Italy, at the University of Rome “La Sapienza”, working on small catalytic RNAs and nuclear-cytoplasmic transport in Xenopus laevis oocytes, in the group of Prof. Irene Bozzoni. 

portrait photo of Sara Buonomo
Sara Buonomo

She pursued her PhD at the Institute for Molecular Pathology (IMP) in Vienna with Prof. Kim Nasmyth, where she studied the role and regulation of sister chromatin cohesion during meiosis in budding yeast and the cell cycle control of the transition between meiosis I and meiosis II. Her postdoctoral work took place at The Rockefeller University in New York, in Prof. Tita de Lange group, investigating the role of a newly identified protein, RIF1, in the DNA damage response in mouse cells.

As a staff scientist at the European Molecular Biology Laboratories (EMBL) in Monterotondo, Rome, Sara started her group exploring the molecular control of the DNA replication timing program in mouse primary fibroblasts and embryonic stem cells. 

Sara moved her group to the University of Edinburgh in October 2015.

Reshma Ravindran Nair Pushkala Kumari, Sophia Tchertkova, Tina Karagyozova, Susanna Alsop, Aneta Jaroskova, Anett Ladanyi and Jose de las Heras


DNA replication is a highly conserved process, crucial to life. Its fundamental principles are the same from bacteria to humans. However, in eukaryotes the increase in genome sizes and the consequent necessity of multiple origins of replication distributed over multiple chromosomes has seen the evolution of several extra layers of regulation. One of the least understood of these layers is the temporal control of DNA replication, present in all eukaryotes. Different genomic regions replicate at specific times during the synthesis phase of the cell cycle (S phase). This replication timing is strictly cell type-specific and must be transmitted from mother to daughter cells to maintain cell type specific identity. Having discovered RIF1 as a key regulator, we are now investigating the molecular mechanisms controlling replication timing, its biological function and how it is connected with other aspects of nuclear function.

We employ a variety of methods, but the heart of our lab are our tissue culture rooms, where we use primary cells, cell lines and stem cells for genome engineering, imaging, biochemistry, genomics, bioinformatics and AI-driven analysis.


Venn diagram of Buonomo lab research

How is the timing of DNA replication controlled?

What identifies the genomic regions that will replicate early or late? We have discovered that late replicating regions are coated by RIF1 and that RIF1-dependent recruitment of Protein Phosphatase 1 is important to delay replication. How does RIF1-PP1 complex executes its functions? How are they targeted to the correct regions?

How is epigenetic identity related to the timing of replication?

The regions of the genome that replicate late in S-phase are characterised by a combination of specific post-translational modifications of histone tails (epigenetic marks) and typically comprise genes that are transcriptionally silent or genomic regions devoid of genes. This genomic compartment, known as heterochromatin, is essential for genome stability and cell identity. Heterochromatin spatial organisation in the nucleus, its late replication and its epigenetic identity are all highly interlinked, each serving as a unique fingerprint of cell identity. We are investigating the molecular mechanisms that coordinate these aspects, aiming ultimately to discover how they direct the specific cell function. Our focus includes various example of heterochromatin, such as the inactive X chromosome or silent endogenous retroviruses.

What is the biological role of the replication timing program?

Our discovery that RIF1, the main regulator of replication timing, plays a number of independent roles in the nucleus has sparked our efforts to create separation of function alleles of Rif1. We are using the guiding principles of human genetics and the precision and versatility of bioengineering tools to overcome technical challenges. In parallel we have initiated the hunt for more regulators of replication timing. Our ultimate goal is to address the big question of why all eukaryotes possess such a robust and redundantly controlled replication timing program. 

Julian Ng-Kee-Kwong, Ben Philps, Fiona N. C. Smith, Aleksandra Sobieska, Naiming Chen, Constance Alabert, Hakan Bilen & Sara C. B. Buonomo (2025) Supervised and unsupervised deep learning-based approaches for studying DNA replication spatiotemporal dynamics. Commun Biol 26, 311. doi.org/10.1038/s42003-025-07744-2

Elin Enervald, Lynn Marie Powell, Lora Boteva, Rossana Foti, Nerea Blanes Ruiz, Gözde Kibar, Agnieszka Piszczek, Fatima Cavaleri, Martin Vingron, Andrea Cerase and Sara B.C. Buonomo (2021) RIF1 and KAP1 differentially regulate the choice of inactive versus active X chromosomes EMBO J. 40: e105865.

Stefano Gnan, Ilya M. Flyamer, Kyle N. Klein, Eleonora Castelli, Jesse L. Turner, Patrick Weber, Andreas Maiser, Elin Enervald, Cristina M. Cardoso, Wendy A. Bickmore, David M. Gilbert and Sara C. B. Buonomo (2021) Nuclear organisation and replication timing are coupled through RIF1-PP1 interaction, Nat. Comm. 12: 2910

Rossana Foti, Stefano Gnan, Daniela Cornacchia, Vishnu Dileep, Aydan Bulut-Karslioglu, Sarah Diehl, Andreas Buness, Felix A. Klein, Wolfgang Huber, Ewan Johnstone, Remco Loos, Paul Bertone, David M. Gilbert, Thomas Manke, Thomas Jenuwein and Sara B.C. Buonomo (2016) Nuclear architecture organized by Rif1 underpins the replication-timing program, Mol. Cell 61, pp. 260-273, -RESEARCH HIGHLIGHT in Nature Reviews Mol. Cell Biol. 17, doi:10.1038/nrm.2016.2.

Daniela Cornacchia, Vishnu Dileep, Jean-Pierre Quivy, Rossana Foti, Federico Tili, Rachel Santarella-Mellwig, Claude Anthony, Genevieve Almouzni, David Gilbert and Sara B.C. Buonomo (2012) Mouse Rif1 is a key regulator of the replication-timing program in mammalian cells EMBO J., 31, pp. 3678-3690. RESEARCH HIGHLIGHT- in EMBO J. 31, 3650-3652.


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