Jos Jonkers

PUM3 is an essential suppressor of replication stress in homologous recombination deficient breast cancer

Most Triple Negative Breast Cancers (TNBCs) are p53 mutant high-grade invasive ductal carcinomas with a basal-like transcriptional programme. A large proportion of TNBCs also have mutation signatures indicating defective homologous recombination (HR) DNA repair. While HR deficiency is mutagenic and oncogenic, it can al...

Models: An Emerging Platform for Translational Cancer Research

CIP2A tetramerization is required for mitotic DNA repair

DNA lesions that persist in mitosis threaten genome stability. These lesions recruit TOPBP1-CIP2A, a complex crucial to tether and process damaged DNA on mitotic chromosomes. Importantly, CIP2A is synthetic lethal in BRCA1/2 mutant cancer cells. However, mechanistic insight into the function of CIP2A is lacking. Here w...

The BRCA1 coiled-coil domain is dispensable for suppression of tandem duplications and tolerance of FANCM loss.

BRCA1-linked cancers contain abundant ~10 kb 'Group 1' tandem duplications (TDs). Group 1 TDs form at a Tus/Ter replication-fork barrier in DNA-end resection-defective mouse embryonic stem (mES) cells lacking Brca1 exon 11. To elucidate how BRCA1 suppresses Group 1 TDs, we analyzed Brca1 coiled-coil (CC)-domain mutants...

Beyond the traditional dish: advanced 3D ex vivo culture platforms for tumor modelling.

The tumor microenvironment (TME) and its complex, dynamic interactions play a pivotal role in cancer development, progression and therapy response. However, faithful recapitulation of the diverse cellular and structural components of the TME in vitro remains a major challenge in cancer research. Traditional 2D cancer c...