Werner syndrome protein, the MRE11 complex and ATR: menage-à-trois in guarding genome stability during DNA replication?
The correct execution of the DNA replication process is crucially import for the maintenance of genome integrity of the cell. Several types of sources, both endogenous and exogenous, can give rise to DNA damage leading to the DNA replication fork arrest. The processes by which replication blockage is sensed by checkpoint sensors and how the pathway leading to resolution of stalled forks is activated are still not completely understood. However, recent emerging evidence suggests that one candidate for a sensor of replication stress is ATR and that, together with a member of RecQ family helicases, Werner syndrome protein (WRN) and MRE11 complex, can collaborate to promote the restarting of DNA synthesis through the resolution of stalled replication forks. Here, we discuss how WRN, the MRE11 complex and the ATR kinase could work together in response to replication blockage to avoid DNA replication fork collapse and genome instability.
Institut Gustave Roussy, CNRS UPR2169, Villejuif, France.
Pietro
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Annapaola
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D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000378:metabolism*; D042822:Genomic Instability; D006801:Humans; D000076228:MRE11 Homologue Protein; D046911:Macromolecular Substances; D008957:Models, Genetic; D014898:Werner Syndrome / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; D046911:Macromolecular Substances; D000076228:MRE11 Homologue Protein