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Mol Cell
2007 Mar 09;255:647-61. doi: 10.1016/j.molcel.2007.01.028.
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Rad50 adenylate kinase activity regulates DNA tethering by Mre11/Rad50 complexes.
Bhaskara V, Dupré A, Lengsfeld B, Hopkins BB, Chan A, Lee JH, Zhang X, Gautier J, Zakian V, Paull TT.
???displayArticle.abstract??? Mre11 and Rad50 are the catalytic components of a highly conserved DNA repair complex that functions in many aspects of DNA metabolism involving double-strand breaks. The ATPase domains in Rad50 are related to the ABC transporter family of ATPases, previously shown to share structural similarities with adenylate kinases. Here we demonstrate that Mre11/Rad50 complexes from three organisms catalyze the reversible adenylate kinase reaction in vitro. Mutation of the conserved signature motif reduces the adenylate kinase activity of Rad50 but does not reduce ATP hydrolysis. This mutant resembles a rad50 null strain with respect to meiosis and telomere maintenance in S. cerevisiae, correlating adenylate kinase activity with in vivo functions. An adenylate kinase inhibitor blocks Mre11/Rad50-dependent DNA tethering in vitro and in cell-free extracts, indicating that adenylate kinase activity by Mre11/Rad50 promotes DNA-DNA associations. We propose a model for Rad50 that incorporates both ATPase and adenylate kinase reactions as critical activities that regulate Rad50 functions.
Alani,
Analysis of wild-type and rad50 mutants of yeast suggests an intimate relationship between meiotic chromosome synapsis and recombination.
1990, Pubmed
Alani,
Analysis of wild-type and rad50 mutants of yeast suggests an intimate relationship between meiotic chromosome synapsis and recombination.
1990,
Pubmed Alexander,
Rap1p telomere association is not required for mitotic stability of a C(3)TA(2) telomere in yeast.
2003,
Pubmed Boulton,
Components of the Ku-dependent non-homologous end-joining pathway are involved in telomeric length maintenance and telomeric silencing.
1998,
Pubmed Chen,
Effect of amino acid substitutions in the rad50 ATP binding domain on DNA double strand break repair in yeast.
2005,
Pubmed Chen,
Promotion of Dnl4-catalyzed DNA end-joining by the Rad50/Mre11/Xrs2 and Hdf1/Hdf2 complexes.
2001,
Pubmed Connelly,
Overexpression, purification, and characterization of the SbcCD protein from Escherichia coli.
1997,
Pubmed Conrad,
RAP1 protein interacts with yeast telomeres in vivo: overproduction alters telomere structure and decreases chromosome stability.
1990,
Pubmed Costanzo,
Mre11 assembles linear DNA fragments into DNA damage signaling complexes.
2004,
Pubmed
,
Xenbase Dean,
Studies on adenine and adenosine metabolism by intact human erythrocytes using high performance liquid chromatography.
1976,
Pubmed de Jager,
DNA end-binding specificity of human Rad50/Mre11 is influenced by ATP.
2002,
Pubmed de Jager,
Human Rad50/Mre11 is a flexible complex that can tether DNA ends.
2001,
Pubmed Diede,
Exonuclease activity is required for sequence addition and Cdc13p loading at a de novo telomere.
2001,
Pubmed Dupré,
Two-step activation of ATM by DNA and the Mre11-Rad50-Nbs1 complex.
2006,
Pubmed
,
Xenbase Gross,
Nucleotide-binding domains of cystic fibrosis transmembrane conductance regulator, an ABC transporter, catalyze adenylate kinase activity but not ATP hydrolysis.
2006,
Pubmed Higgins,
The ATP switch model for ABC transporters.
2004,
Pubmed Holland,
ABC-ATPases, adaptable energy generators fuelling transmembrane movement of a variety of molecules in organisms from bacteria to humans.
1999,
Pubmed Hopfner,
Structural biology of Rad50 ATPase: ATP-driven conformational control in DNA double-strand break repair and the ABC-ATPase superfamily.
2000,
Pubmed Hopfner,
The Rad50 zinc-hook is a structure joining Mre11 complexes in DNA recombination and repair.
2002,
Pubmed Hyde,
Structural model of ATP-binding proteins associated with cystic fibrosis, multidrug resistance and bacterial transport.
1990,
Pubmed Kaye,
DNA breaks promote genomic instability by impeding proper chromosome segregation.
2004,
Pubmed Kerem,
Identification of the cystic fibrosis gene: genetic analysis.
1989,
Pubmed Krogh,
Recombination proteins in yeast.
2004,
Pubmed Lavin,
The Mre11 complex and ATM: a two-way functional interaction in recognising and signaling DNA double strand breaks.
2004,
Pubmed Lee,
ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex.
2005,
Pubmed Lee,
Complementation between N-terminal Saccharomyces cerevisiae mre11 alleles in DNA repair and telomere length maintenance.
2002,
Pubmed Lee,
Regulation of Mre11/Rad50 by Nbs1: effects on nucleotide-dependent DNA binding and association with ataxia-telangiectasia-like disorder mutant complexes.
2003,
Pubmed Lienhard,
P 1 ,P 5 -Di(adenosine-5')pentaphosphate, a potent multisubstrate inhibitor of adenylate kinase.
1973,
Pubmed Lisby,
Choreography of the DNA damage response: spatiotemporal relationships among checkpoint and repair proteins.
2004,
Pubmed Lobachev,
Chromosome fragmentation after induction of a double-strand break is an active process prevented by the RMX repair complex.
2004,
Pubmed Menze,
Depression of cell metabolism and proliferation by membrane-permeable and -impermeable modulators: role for AMP-to-ATP ratio.
2005,
Pubmed Moncalian,
The rad50 signature motif: essential to ATP binding and biological function.
2004,
Pubmed Moore,
Cell cycle and genetic requirements of two pathways of nonhomologous end-joining repair of double-strand breaks in Saccharomyces cerevisiae.
1996,
Pubmed Moreau,
The nuclease activity of Mre11 is required for meiosis but not for mating type switching, end joining, or telomere maintenance.
1999,
Pubmed Paull,
Nbs1 potentiates ATP-driven DNA unwinding and endonuclease cleavage by the Mre11/Rad50 complex.
1999,
Pubmed Randak,
A recombinant polypeptide model of the second nucleotide-binding fold of the cystic fibrosis transmembrane conductance regulator functions as an active ATPase, GTPase and adenylate kinase.
1997,
Pubmed Randak,
An intrinsic adenylate kinase activity regulates gating of the ABC transporter CFTR.
2003,
Pubmed Raymond,
RAD50 protein of S.cerevisiae exhibits ATP-dependent DNA binding.
1993,
Pubmed Robertson,
Isolation and characterization of Xenopus ATM (X-ATM): expression, localization, and complex formation during oogenesis and early development.
1999,
Pubmed
,
Xenbase Shroff,
Distribution and dynamics of chromatin modification induced by a defined DNA double-strand break.
2004,
Pubmed Smith,
Suppression of gross chromosomal rearrangements by the multiple functions of the Mre11-Rad50-Xrs2 complex in Saccharomyces cerevisiae.
2005,
Pubmed Smythe,
Systems for the study of nuclear assembly, DNA replication, and nuclear breakdown in Xenopus laevis egg extracts.
1991,
Pubmed
,
Xenbase Stracker,
The Mre11 complex and the metabolism of chromosome breaks: the importance of communicating and holding things together.
2004,
Pubmed Trujillo,
Yeast xrs2 binds DNA and helps target rad50 and mre11 to DNA ends.
2003,
Pubmed Tsukamoto,
The role of the Mre11-Rad50-Xrs2 complex in telomerase- mediated lengthening of Saccharomyces cerevisiae telomeres.
2001,
Pubmed Williams,
Learning our ABCs: Rad50 directs MRN repair functions via adenylate kinase activity from the conserved ATP binding cassette.
2007,
Pubmed Yan,
Nucleoside monophosphate kinases: structure, mechanism, and substrate specificity.
1999,
Pubmed Zhang,
The Mre11/Rad50/Xrs2 complex and non-homologous end-joining of incompatible ends in S. cerevisiae.
2005,
Pubmed
