title: Double functions for the Mre11 complex during DNA double-strand break repair and replication.
abstract: Defining the factors that lead to genomic instability is one of the most important fields in cancer biology. DNA damage can arise from exogenous sources or as a result of normal cellular metabolism. Regardless of the cause, when damaged DNA is not properly repaired the genome acquires mutation(s). Under normal circumstances, to prevent such chromosome instability the cell activates the checkpoint response, which inhibits cell cycle progression until DNA repair is complete. The Mre11 complex is formed by three components: Mre11, Rad50, and Nbs1/Xrs2 and is involved in the signaling pathways that lead to both checkpoint activation and DNA repair. In response to DNA damage two functions of the complex will be discussed, one involves its role in initiating kinase activation and the second involves its ability to tether and link DNA strands. This review will highlight the functions of the Mre11 complex during the process of DNA double strand break recognition and repair, and during the process of replication. Understanding how the Mre11 complex is working at the molecular level is important for understanding why disruptions in components of the complex lead to genomic instability and cancer predisposition syndromes in humans.
authors.affiliation: Institut Curie, Centre de Recherche, UMR7147 CNRS-Institut Curie-Université P. and M. Curie, 26 rue d'Ulm, 75248, Paris Cedex 05, France. valerie.borde@curie.fr
authors.forename: Valérie
authors.initials: V
authors.lastname: Borde
authors.forename: Jennifer
authors.initials: J
authors.lastname: Cobb
mesh_terms: D000818:Animals; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000502:physiology*; D003851:Deoxyribonucleases / Q000502:physiology*; D006801:Humans; D000076228:MRE11 Homologue Protein
chemical_list: D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; D003851:Deoxyribonucleases; D000076228:MRE11 Homologue Protein