Molecular Oncology Programme

DNA Replication Group

Group Leader:  Juan Méndez

Up to two thirds of the total mutations detected in tumours are caused by inaccurate DNA replication. Our laboratory studies the process of DNA replication using a combination of biochemistry, cell biology and mouse genetics. Our current interests include: (1) the genetic and epigenetic elements that define replication origins; (2) the cellular responses to replicative stress (RS) caused by endogenous elements (e.g. natural decay of DNA; collisions between replication and transcription proteins) or exogenous factors such as UV radiation or DNA-damaging chemical agents. One of the responses to RS is the activation of ‘dormant’ origins, whose regulation remains poorly understood; (3) the mechanisms that limit DNA replication to only one round in each cell cycle, and the physiological consequences of their malfunction; and (4) the role of PrimPol, a recently characterised enzyme with primase and polymerase activities, in the ‘tolerance’ mechanisms that enable replication through damaged DNA.