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Mol Cell
2013 Feb 21;494:657-67. doi: 10.1016/j.molcel.2012.11.020.
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Activation of DSB processing requires phosphorylation of CtIP by ATR.
Peterson SE
,
Li Y
,
Wu-Baer F
,
Chait BT
,
Baer R
,
Yan H
,
Gottesman ME
,
Gautier J
.
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DNA double-strand breaks (DSBs) activate a DNA damage response (DDR) that coordinates checkpoint pathways with DNA repair. ATM and ATR kinases are activated sequentially. Homology-directed repair (HDR) is initiated by resection of DSBs to generate 3' single-stranded DNA overhangs. How resection and HDR are activated during DDR is not known, nor are the roles of ATM and ATR in HDR. Here, we show that CtIP undergoes ATR-dependent hyperphosphorylation in response to DSBs. ATR phosphorylates an invariant threonine, T818 of Xenopus CtIP (T859 in human). Nonphosphorylatable CtIP (T818A) does not bind to chromatin or initiate resection. Our data support a model in which ATM activity is required for an early step in resection, leading to ATR activation, CtIP-T818 phosphorylation, and accumulation of CtIP on chromatin. Chromatin binding by modified CtIP precedes extensive resection and full checkpoint activation.
Akamatsu,
Molecular characterization of the role of the Schizosaccharomyces pombe nip1+/ctp1+ gene in DNA double-strand break repair in association with the Mre11-Rad50-Nbs1 complex.
2008, Pubmed
Akamatsu,
Molecular characterization of the role of the Schizosaccharomyces pombe nip1+/ctp1+ gene in DNA double-strand break repair in association with the Mre11-Rad50-Nbs1 complex.
2008,
Pubmed
Alderton,
Seckel syndrome exhibits cellular features demonstrating defects in the ATR-signalling pathway.
2004,
Pubmed
Barker,
Identification of mammalian proteins cross-linked to DNA by ionizing radiation.
2005,
Pubmed
Baroni,
The functions of budding yeast Sae2 in the DNA damage response require Mec1- and Tel1-dependent phosphorylation.
2004,
Pubmed
Barr,
ATR kinase activity regulates the intranuclear translocation of ATR and RPA following ionizing radiation.
2003,
Pubmed
Budd,
Interplay of Mre11 nuclease with Dna2 plus Sgs1 in Rad51-dependent recombinational repair.
2009,
Pubmed
Bunting,
53BP1 inhibits homologous recombination in Brca1-deficient cells by blocking resection of DNA breaks.
2010,
Pubmed
Byun,
Functional uncoupling of MCM helicase and DNA polymerase activities activates the ATR-dependent checkpoint.
2005,
Pubmed
,
Xenbase
Cejka,
DNA end resection by Dna2-Sgs1-RPA and its stimulation by Top3-Rmi1 and Mre11-Rad50-Xrs2.
2010,
Pubmed
Cimprich,
ATR: an essential regulator of genome integrity.
2008,
Pubmed
Costanzo,
An ATR- and Cdc7-dependent DNA damage checkpoint that inhibits initiation of DNA replication.
2003,
Pubmed
,
Xenbase
Cuadrado,
ATM regulates ATR chromatin loading in response to DNA double-strand breaks.
2006,
Pubmed
Derheimer,
Multiple roles of ATM in monitoring and maintaining DNA integrity.
2010,
Pubmed
Eid,
DNA end resection by CtIP and exonuclease 1 prevents genomic instability.
2010,
Pubmed
Garner,
Studying the DNA damage response using in vitro model systems.
2009,
Pubmed
,
Xenbase
Hartsuiker,
Distinct requirements for the Rad32(Mre11) nuclease and Ctp1(CtIP) in the removal of covalently bound topoisomerase I and II from DNA.
2009,
Pubmed
Hartsuiker,
Ctp1CtIP and Rad32Mre11 nuclease activity are required for Rec12Spo11 removal, but Rec12Spo11 removal is dispensable for other MRN-dependent meiotic functions.
2009,
Pubmed
Henner,
gamma Ray induced deoxyribonucleic acid strand breaks. 3' Glycolate termini.
1983,
Pubmed
Hickson,
Identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM.
2004,
Pubmed
Hoeijmakers,
DNA damage, aging, and cancer.
2009,
Pubmed
Huertas,
Human CtIP mediates cell cycle control of DNA end resection and double strand break repair.
2009,
Pubmed
Jazayeri,
ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks.
2006,
Pubmed
Jazayeri,
Mre11-Rad50-Nbs1-dependent processing of DNA breaks generates oligonucleotides that stimulate ATM activity.
2008,
Pubmed
,
Xenbase
Keeney,
Initiation of meiotic recombination by formation of DNA double-strand breaks: mechanism and regulation.
2006,
Pubmed
Kim,
Substrate specificities and identification of putative substrates of ATM kinase family members.
1999,
Pubmed
Langerak,
Release of Ku and MRN from DNA ends by Mre11 nuclease activity and Ctp1 is required for homologous recombination repair of double-strand breaks.
2011,
Pubmed
Lawley,
DNA adducts from chemotherapeutic agents.
1996,
Pubmed
Leahy,
Identification of a highly potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor (NU7441) by screening of chromenone libraries.
2004,
Pubmed
Lee,
Activation and regulation of ATM kinase activity in response to DNA double-strand breaks.
2007,
Pubmed
Lewis,
Differential suppression of DNA repair deficiencies of Yeast rad50, mre11 and xrs2 mutants by EXO1 and TLC1 (the RNA component of telomerase).
2002,
Pubmed
Li,
Functional link of BRCA1 and ataxia telangiectasia gene product in DNA damage response.
2000,
Pubmed
Liao,
Identification of the Xenopus DNA2 protein as a major nuclease for the 5'->3' strand-specific processing of DNA ends.
2008,
Pubmed
,
Xenbase
Liao,
Mechanistic analysis of Xenopus EXO1's function in 5'-strand resection at DNA double-strand breaks.
2011,
Pubmed
,
Xenbase
Liao,
Analysis of MRE11's function in the 5'-->3' processing of DNA double-strand breaks.
2012,
Pubmed
,
Xenbase
Limbo,
Ctp1 is a cell-cycle-regulated protein that functions with Mre11 complex to control double-strand break repair by homologous recombination.
2007,
Pubmed
Liu,
ATR autophosphorylation as a molecular switch for checkpoint activation.
2011,
Pubmed
Lloyd,
A supramodular FHA/BRCT-repeat architecture mediates Nbs1 adaptor function in response to DNA damage.
2009,
Pubmed
Matsuoka,
ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.
2007,
Pubmed
McKee,
A general method for identifying recessive diploid-specific mutations in Saccharomyces cerevisiae, its application to the isolation of mutants blocked at intermediate stages of meiotic prophase and characterization of a new gene SAE2.
1997,
Pubmed
Milman,
Meiotic DNA double-strand break repair requires two nucleases, MRN and Ctp1, to produce a single size class of Rec12 (Spo11)-oligonucleotide complexes.
2009,
Pubmed
Mimitou,
Sae2, Exo1 and Sgs1 collaborate in DNA double-strand break processing.
2008,
Pubmed
Moreau,
Overlapping functions of the Saccharomyces cerevisiae Mre11, Exo1 and Rad27 nucleases in DNA metabolism.
2001,
Pubmed
Mu,
A proteomic analysis of ataxia telangiectasia-mutated (ATM)/ATM-Rad3-related (ATR) substrates identifies the ubiquitin-proteasome system as a regulator for DNA damage checkpoints.
2007,
Pubmed
Myers,
Rapid activation of ATR by ionizing radiation requires ATM and Mre11.
2006,
Pubmed
Nakamura,
Collaborative action of Brca1 and CtIP in elimination of covalent modifications from double-strand breaks to facilitate subsequent break repair.
2010,
Pubmed
Nam,
ATR signalling: more than meeting at the fork.
2011,
Pubmed
Neale,
Endonucleolytic processing of covalent protein-linked DNA double-strand breaks.
2005,
Pubmed
O'Driscoll,
A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome.
2003,
Pubmed
Paull,
Making the best of the loose ends: Mre11/Rad50 complexes and Sae2 promote DNA double-strand break resection.
2010,
Pubmed
Peterson,
Cdk1 uncouples CtIP-dependent resection and Rad51 filament formation during M-phase double-strand break repair.
2011,
Pubmed
,
Xenbase
Prinz,
Isolation of COM1, a new gene required to complete meiotic double-strand break-induced recombination in Saccharomyces cerevisiae.
1997,
Pubmed
Qvist,
CtIP Mutations Cause Seckel and Jawad Syndromes.
2011,
Pubmed
Rothenberg,
Ctp1 and the MRN-complex are required for endonucleolytic Rec12 removal with release of a single class of oligonucleotides in fission yeast.
2009,
Pubmed
Sartori,
Human CtIP promotes DNA end resection.
2007,
Pubmed
Shim,
Saccharomyces cerevisiae Mre11/Rad50/Xrs2 and Ku proteins regulate association of Exo1 and Dna2 with DNA breaks.
2010,
Pubmed
Shiotani,
Single-stranded DNA orchestrates an ATM-to-ATR switch at DNA breaks.
2009,
Pubmed
Shrivastav,
Regulation of DNA double-strand break repair pathway choice.
2008,
Pubmed
Srinivasan,
Study of cell cycle checkpoints using Xenopus cell-free extracts.
2011,
Pubmed
,
Xenbase
Sun,
Human Ku70/80 protein blocks exonuclease 1-mediated DNA resection in the presence of human Mre11 or Mre11/Rad50 protein complex.
2012,
Pubmed
Symington,
Double-strand break end resection and repair pathway choice.
2011,
Pubmed
Taylor,
The Mre11/Rad50/Nbs1 complex functions in resection-based DNA end joining in Xenopus laevis.
2010,
Pubmed
,
Xenbase
Toledo,
A cell-based screen identifies ATR inhibitors with synthetic lethal properties for cancer-associated mutations.
2011,
Pubmed
Tomimatsu,
Exo1 plays a major role in DNA end resection in humans and influences double-strand break repair and damage signaling decisions.
2012,
Pubmed
Williams,
Mre11 dimers coordinate DNA end bridging and nuclease processing in double-strand-break repair.
2008,
Pubmed
Williams,
Nbs1 flexibly tethers Ctp1 and Mre11-Rad50 to coordinate DNA double-strand break processing and repair.
2009,
Pubmed
Wu-Baer,
Effect of DNA damage on a BRCA1 complex.
2001,
Pubmed
Yan,
Replication protein A promotes 5'-->3' end processing during homology-dependent DNA double-strand break repair.
2011,
Pubmed
,
Xenbase
You,
CtIP links DNA double-strand break sensing to resection.
2009,
Pubmed
,
Xenbase
Zhu,
Sgs1 helicase and two nucleases Dna2 and Exo1 resect DNA double-strand break ends.
2008,
Pubmed
Zou,
Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes.
2003,
Pubmed
