Rad50S alleles of the Mre11 complex: Questions answered and questions raised Journal Article


Authors: Usui, T.; Petrini, J. H. J.; Morales, M.
Article Title: Rad50S alleles of the Mre11 complex: Questions answered and questions raised
Abstract: We find that Rad50S mutations in yeast and mammals exhibit constitutive PIKK (PI3-kinase like kinase)-dependent signaling [T. Usui, H. Ogawa, J.H. Petrini, A DNA damage response pathway controlled by Tel1 and the Mre11 complex. Mol. Cell 7 (2001) 1255-1266.; M. Morales, J.W. Theunissen, C.F. Kim, R. Kitagawa, M.B. Kastan, J.H. Petrini, The Rad50S allele promotes ATM-dependent DNA damage responses and suppresses ATM deficiency: implications for the Mre11 complex as a DNA damage sensor. Genes Dev. 19 (2005) 3043-4354.]. The signaling depends on Mre11 complex functions, consistent with its role as a DNA damage sensor. Rad50S is distinct from hypomorphic mutations of Mre11 and Nbs1 in mammals [M. Morales, J.W. Theunissen, C.F. Kim, R. Kitagawa, M.B. Kastan, J.H. Petrini, The Rad50S allele promotes ATM-dependent DNA damage responses and suppresses ATM deficiency: implications for the Mre11 complex as a DNA damage sensor. Genes Dev. 19 (2005) 3043-3054.; J.P. Carney, R.S. Maser, H. Olivares, E.M. Davis, Le M. Beau, J.R. Yates, III, L. Hays, W.F. Morgan, J.H. Petrini, The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response. Cell 93 (1998) 477-486.; G.S. Stewart, R.S. Maser, T. Stankovic, D.A. Bressan, M.I. Kaplan, N.G. Jaspers, A. Raams, P.J. Byrd, J.H. Petrini, A.M. Taylor, The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder. Cell 99 (1999) 577-587.; B.R. Williams, O.K. Mirzoeva, W.F. Morgan, J. Lin, W. Dunnick, J.H. Petrini, A murine model of nijmegen breakage syndrome. Curr. Biol. 12 (2002) 648-653.; J.W. Theunissen, M.I. Kaplan, P.A. Hunt, B.R. Williams, D.O. Ferguson, F.W. Alt, J.H. Petrini, Checkpoint failure and chromosomal instability without lymphomagenesis in Mre11(ATLD1/ATLD1) mice. Mol. Cell 12 (2003) 1511-1523.] and the Mre11 complex deficiency in yeast [T. Usui, H. Ogawa, J.H. Petrini, A DNA damage response pathway controlled by Tel1 and the Mre11 complex. Mol. Cell 7 (2001) 1255-1266.; D'D. Amours, S.P. Jackson, The yeast Xrs2 complex functions in S phase checkpoint regulation. Genes Dev. 15 (2001) 2238-49. [7]; M. Grenon, C. Gilbert, N.F. Lowndes, Checkpoint activation in response to double-strand breaks requires the Mre11/Rad50/Xrs2 complex. Nat. Cell Biol. 3 (2001) 844-847. [8]] where the signaling is compromised. Herein, we describe evidence for chronic signaling by Rad50S and discuss possible mechanisms. © 2006 Elsevier Inc. All rights reserved.
Keywords: signal transduction; protein expression; protein phosphorylation; gene mutation; dna-binding proteins; review; nonhuman; dna replication; protein function; phenotype; mammalia; animals; mre11 protein; rad50 protein; dna damage; cell cycle s phase; dna repair; apoptosis; enzyme activation; enzyme substrate; phosphatidylinositol 3 kinase; carcinogenesis; dna strand breakage; molecular mechanics; double stranded dna; genetic recombination; murinae; atm protein; chromosomal instability; nijmegen breakage syndrome; checkpoint kinase 2; saccharomyces cerevisiae proteins; cell cycle regulation; atr protein; checkpoints; ataxia telangiectasia; endodeoxyribonucleases; exodeoxyribonucleases; mre11 complex; pikk signaling; rad50s rad50s alleles
Journal Title: Experimental Cell Research
Volume: 312
Issue: 14
ISSN: 0014-4827
Publisher: Elsevier Inc.  
Date Published: 2006-08-15
Start Page: 2694
End Page: 2699
Language: English
DOI: 10.1016/j.yexcr.2006.06.013
PUBMED: 16857186
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 15" - "Export Date: 4 June 2012" - "CODEN: ECREA" - "Source: Scopus"
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MSK Authors
  1. Takehiko Usui
    6 Usui
  2. John Petrini
    79 Petrini