Every cell faces the enormous challenge of copying and maintaining its DNA. The genome—the complete set of genetic instructions—must be faithfully passed from one generation to the next. But along the way, DNA is constantly under attack. Errors can occur during replication, environmental factors like UV light can cause damage, and even normal cellular processes can introduce breaks or mutations.
Genome stability refers to the cell’s ability to protect, repair, and accurately duplicate its DNA despite these challenges. When these protective systems fail, the consequences can be serious: mutations accumulate, chromosomes break or rearrange, and diseases such as cancer can arise.
My research investigates the genetic “safety nets” that promote genome stability. Cells use checkpoints to sense when something has gone wrong, DNA repair pathways to fix the damage, and backup circuits that ensure survival even when the main systems falter. By studying these pathways, I aim to understand not just how cells preserve their genetic integrity, but also how they adapt under stress—for example, when exposed to drugs that target DNA replication.
Selected Publications:
- Herzog M et al., Nucleic Acids Research (2021)
This study investigates the mutagenic effects of cancer-associated DNA polymerase ε alleles, revealing that certain mutations lead to ultra-mutagenesis in yeast models. The findings enhance understanding of how specific polymerase variants contribute to tumorigenesis. Accessible summary - Puddu F et al., Nature (2019): This study systematically analyzed the genome-wide consequences of deleting nearly every non-essential gene in Saccharomyces cerevisiae, revealing how gene loss leads to specific genomic alterations and uncovering the intricate interactions between nuclear and mitochondrial genome stability. Accessible summary
- Puddu et al., EMBO Reports (2017)
This study identifies chromatin factors that influence cellular sensitivity to camptothecin, a DNA-damaging agent, highlighting how chromatin structure and modifications can affect the response to DNA damage. Accessible summary - Puddu et al., EMBO Journal (2015): This study employs synthetic viability screening to elucidate the role of Sae2 in DNA repair, identifying genetic interactions that rescue the lethal effects of Sae2 deficiency and providing insights into its function in DNA double-strand break repair. Accessible summary
- Puddu F, et al (2011) This study identifies two distinct pathways through which the Mec1 protein is activated in response to replication stress, highlighting the roles of the 9-1-1 complex and DNA polymerase ε in maintaining genome stability. Accessible summary
👉 Related pages:
- Synthetic viability: how backup pathways can rescue cells when key genes are lost
- SGV: the role of genetic variation in shaping genome stability