The Mre11 complex and the metabolism of chromosome breaks: The importance of communicating and holding things together Journal Article
| Authors: | Stracker, T. H.; Theunissen, J. W. F.; Morales, M.; Petrini, J. H. J. |
| Article Title: | The Mre11 complex and the metabolism of chromosome breaks: The importance of communicating and holding things together |
| Abstract: | 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. © 2004 Elsevier B.V. All rights reserved. |
| Keywords: | gene mutation; mutation; dna-binding proteins; review; nonhuman; neoplasms; dna recombination; phenotype; meiosis; mammalia; animals; cell cycle proteins; mice; mre11 protein; rad50 protein; cell viability; dna damage; cell survival; cell cycle; dna repair; cell growth; alleles; carcinogenesis; chromatid; nuclear proteins; dna; amino acid sequence; molecular sequence data; saccharomyces cerevisiae; recombination, genetic; dna repair enzymes; chromosome breakage; genetic stability; genome; models, genetic; protein deficiency; yeast; dna, single-stranded; genetic disorder; chromosomes; checkpoints; mammal cell; atm; experimental model; mre11 complex; double strand breaks; humans; human; priority journal |
| Journal Title: | DNA Repair |
| Volume: | 3 |
| Issue: | 8-9 |
| ISSN: | 1568-7864 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2004-08-01 |
| Start Page: | 845 |
| End Page: | 854 |
| Language: | English |
| DOI: | 10.1016/j.dnarep.2004.03.014 |
| PROVIDER: | scopus |
| PUBMED: | 15279769 |
| DOI/URL: | |
| Notes: | DNA Repair -- Cited By (since 1996):195 -- Export Date: 16 June 2014 -- CODEN: DRNEA -- Source: Scopus |
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