The Mre11 complex and the metabolism of chromosome breaks: the importance of communicating and holding things together.
The conserved Mre11 complex (Mre11, Rad50, and Nbs1) plays a role in each aspect of chromosome break metabolism. The complex acts as a break sensor and functions in the activation and propagation of signaling pathways that govern cell cycle checkpoint functions in response to DNA damage. In addition, the Mre11 complex influences recombinational DNA repair through promoting recombination between sister chromatids. The Mre11 complex is required for mammalian cell viability but hypomorphic mutants of Mre11 and Nbs1 have been identified in human genetic instability disorders. These hypomorphic mutations, as well as those identified in yeast, have provided a benchmark for establishing mouse models of Mre11 complex deficiency. In addition to consideration of Mre11 complex functions in human cells and yeast, this review will discuss the characterization of mouse models and insight gleaned from those models regarding the metabolism of chromosome breaks. The current picture of break metabolism supports a central role for the Mre11 complex at the interface of chromosome stability and the regulation of cell growth. Further genetic analysis of the Mre11 complex will be an invaluable tool for dissecting its function on an organismal level and determining its role in the prevention of malignancy.
Molecular Biology Program, Memorial Sloan Kettering Cancer Center and Cornell University Graduate School of Medical Sciences, New York, NY 10021, USA.
Travis H
TH
Stracker
Jan-Willem F
JW
Theunissen
Monica
M
Morales
John H J
JH
Petrini
D017766:Acid Anhydride Hydrolases; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000502:physiology*; D002470:Cell Survival; D002875:Chromosomes / Q000648:ultrastructure*; D004247:DNA / Q000235:genetics; D004249:DNA Damage; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000502:physiology; D004277:DNA, Single-Stranded / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D016678:Genome; D006801:Humans; D000076228:MRE11 Homologue Protein; D008540:Meiosis; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D009369:Neoplasms / Q000209:etiology; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology*; D010641:Phenotype; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000378:metabolism
D018797:Cell Cycle Proteins; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; C512689:Mre11a protein, mouse; C112156:NBN protein, human; D009687:Nuclear Proteins; D004247:DNA; D000076228:MRE11 Homologue Protein; D017766:Acid Anhydride Hydrolases; C112158:RAD50 protein, human; D045643:DNA Repair Enzymes