Molecular Oncology Programme

DNA Replication Group

Group Leader:  Juan Méndez

Our laboratory studies the molecular mechanisms that underlie genomic duplication in mammalian cells. The ‘replisome’ complex in charge of DNA replication encounters natural obstacles (e.g. unusual DNA structures, collisions with transcription proteins), as well as exogenous challenges such as ionising radiation, UV light and chemicals that modify the DNA structure and block DNA polymerases. The situations in which replication forks are forced to slow down, stall or collapse are generically referred to as replicative stress (RS). Our Group investigates the ‘DNA damage tolerance’ pathways that facilitate DNA replication in the presence of RS or damaged DNA. In recent years, we have identified 2 mechanisms that counteract RS: (1) the conditional activation of dormant replication origins; (2) the participation of PrimPol, a primase-polymerase enzyme, in the restart of stalled forks. We continue to characterise the different cellular responses to RS (FIGURE 1).