DNA recombination and cancer

To maintain genomic stability, cells are equipped with efficient ways of repairing these breaks via several mechanisms. BRCA1 is a key protein for the repair of DSBs via Homologous Recombination (HR). This faithful mechanism of repair uses the information of the sister chromatid for repair during S and G2 of the cell cycle. BRCA1 mutations occur in a wide variety of tumours, including hereditary forms of breast and ovarian cancer, but also lung and gastric cancer. Next to many truncating mutations, leading to a fully dysfunctional BRCA1, many missense mutations and also variants of unknown significance have been identified in tumours.  BRCA1-mutated tumours are characterised by gross chromosomal instability. However, how all these different mutations in BRCA1 are involved in cancer development and therapy response is often still unclear.

One of the main complexities in studying BRCA1 function is the fact that it forms several multi-protein complexes via its different protein domains, most of them stimulating HR, but others – counterintuitively – inhibiting HR. The main question in my lab is to better understand how all these different BRCA1-complexes cooperate to maintain genomic stability and how mutations disrupting single complexes affect tumorigenesis. My lab uses a combination of systematic approaches such as genome-wide CRISPR-Cas9 screens and proteomics, with dedicated functional assays in mammalian cell systems to study the mechanisms of BRCA1 function.

Dr. Sylvie M. Noordermeer
Principal Investigator / Associate Professor

Bas Molenaar                     
Researcher

Marta San Martín Alonso
Researcher

Timo J. Wendel                     
Researcher

Venda Mangkusaputra     
PhD student

Anne Schreuder                  
PhD student

Veronica Garzero                
Research technician