The Role of JNK Signalling in Responses to Oxidative DNA Damage

The production of reactive oxygen species is a normal part of cell physiology, but many internal and external stimuli are able to trigger the production of excess levels of oxidants that are potentially damaging. The threat of oxidative damage is particularly significant to DNA, as damaged bases can interfere with replication to generate lasting mutations. Signalling through the JNK pathway is a key cellular response to oxidative damage. Depending on the intensity and duration of the damage signal, JNK signalling can lead to distinct alternative responses including DNA repair, anti-oxidant production or cell death. These responses are highly relevant to cancer therapy, as tumours are often under oxidative stress that produces elevated JNK levels and therapy often involves inducing DNA damage with the intention of driving cell death. In this review we examine the causes and consequences of JNK activation that relate to oxidative DNA damage, with a focus on the potential therapeutic implications.