Rad50 is dispensable for the maintenance and viability of postmitotic tissues Journal Article

Authors: Adelman, C. A.; De, Saurav; Petrini, J. H. J.
Article Title: Rad50 is dispensable for the maintenance and viability of postmitotic tissues
Abstract: The majority of spontaneous chromosome breakage occurs during the process of DNA replication. Homologous recombination is the primary mechanism of repair of such damage, which probably accounts for the fact that it is essential for genome integrity and viability in mammalian cells. The Mre11 complex plays diverse roles in the maintenance of genomic integrity, influencing homologous recombination, checkpoint activation, and telomere maintenance. The complex is essential for cellular viability, but given its myriad influences on genomic integrity, the mechanistic basis for the nonviability of Mre11 complex-deficient cells has not been defined. In this study we generated mice carrying a conditional allele of Rad50 and examined the effects of Rad50 deficiency in proliferative and nonproliferative settings. Depletion of Rad50 in cultured cells caused extensive DNA damage and death within 3 to 5 days of Rad50 deletion. This was not associated with gross telomere dysfunction, suggesting that the telomeric functions of the Mre11 complex are not required for viability. Rad50 was also dispensable for the viability of quiescent liver and postmitotic Purkinje cells of the cerebellum. These findings support the idea that the essential functions of the Mre11 complex are associated with DNA replication and further suggest that homologous recombination is not essential in nondividing cells. Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Keywords: controlled study; gene deletion; dna-binding proteins; nonhuman; dna replication; cell proliferation; mitosis; animal cell; mouse; telomere; mammalia; animals; mice; mice, knockout; actin; mre11 protein; rad50 protein; allele; animal tissue; cell death; cell viability; cerebellum; dna damage; gene; homologous recombination; purkinje cell; rad50 gene; atp-binding cassette transporters; bone marrow cells; cell survival; cells, cultured; gene targeting; hepatocytes; in situ hybridization, fluorescence; purkinje cells; mus
Journal Title: Molecular and Cellular Biology
Volume: 29
Issue: 2
ISSN: 0270-7306
Publisher: American Society for Microbiology  
Date Published: 2009-01-01
Start Page: 483
End Page: 492
Language: English
DOI: 10.1128/mcb.01525-08
PUBMED: 19001091
PROVIDER: scopus
PMCID: PMC2612516
Notes: --- - "Cited By (since 1996): 4" - "Export Date: 30 November 2010" - "CODEN: MCEBD" - "Source: Scopus"
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MSK Authors
  1. John Petrini
    76 Petrini
  2. Saurav De
    5 De