Werner syndrome (WS) is an autosomal recessive disease that predisposes individuals toa wide range of cancers. The gene mutated in WS, WRN, encodes a member of the RecQfamily of DNA helicases. The precise DNA metabolic processes in which WRN participatesremain to be elucidated. However, it has been proposed that WRN might play an importantrole in the maintenance of genetic stability during DNA replication, possibly cooperatingwith other proteins. Here, we show that, following DNA replication arrest, WRN associatesand colocalises with the MRE11 complex at PCNA sites. We also provide evidence thatboth WRN/MRE11 complex association and proper WRN relocalisation after HU treatmentrequire a functional MRE11 complex. We demonstrate that mutations altering thefunctionality of WRN or that of the MRE11 complex result in chromosomal breakage duringDNA replication and enhanced cell death following replication arrest. Finally, we show thatthe DNA breakage in replicating cells and apoptosis observed in WS are not enhanced byconcomitant knock down of MRE11 by RNAi, indicating that WRN and MRE11 complexact in a common pathway. These results suggest a functional relationship between WRNand the MRE11 complex in response to replication fork arrest, disclosing a common actionof WRN and the MRE11 complex in the pathway(s) preserving genome stability duringDNA replication.