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Literature DB >> 19709933

PIKK-dependent phosphorylation of Mre11 induces MRN complex inactivation by disassembly from chromatin.

Michela Di Virgilio¹, Carol Y Ying, Jean Gautier.

Abstract

The role of Mre11 phosphorylation in the cellular response to DNA double-strand breaks (DSBs) is not well understood. Here, we show that phosphorylation of Mre11 at SQ/TQ motifs by PIKKs (PI3 Kinase-related Kinases) induces MRN (Mre11-Rad50-Nbs1) complex dissociation from chromatin by reducing Mre11 affinity for DNA. Whereas phosphorylation of Mre11 at these residues is not required for DSB-induced ATM (Ataxia-Telangiectasia mutated) activation, abrogation of Mre11 dephosphorylation impairs ATM signaling. Our study provides a functional characterization of the DNA damage-induced Mre11 phosphorylation, and suggests that MRN inactivation participates in the down-regulation of damage signaling during checkpoint recovery following DSB repair.

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Year: 2009 PMID： 19709933 PMCID： PMC2764007 DOI： 10.1016/j.dnarep.2009.07.006

Source DB: PubMed Journal: DNA Repair (Amst) ISSN： 1568-7856

79 in total

1. A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recovery.

Authors: Michael-Christopher Keogh; Jung-Ae Kim; Michael Downey; Jeffrey Fillingham; Dipanjan Chowdhury; Jacob C Harrison; Megumi Onishi; Nira Datta; Sarah Galicia; Andrew Emili; Judy Lieberman; Xuetong Shen; Stephen Buratowski; James E Haber; Daniel Durocher; Jack F Greenblatt; Nevan J Krogan
Journal: Nature Date: 2005-11-20 Impact factor: 49.962

2. Two-step activation of ATM by DNA and the Mre11-Rad50-Nbs1 complex.

Authors: Aude Dupré; Louise Boyer-Chatenet; Jean Gautier
Journal: Nat Struct Mol Biol Date: 2006-04-23 Impact factor: 15.369

Review 3. Signaling networks controlled by the MRN complex and MDC1 during early DNA damage responses.

Authors: Ja-Eun Kim; Katherine Minter-Dykhouse; Junjie Chen
Journal: Mol Carcinog Date: 2006-06 Impact factor: 4.784

4. Purification and biochemical characterization of ataxia-telangiectasia mutated and Mre11/Rad50/Nbs1.

Authors: Ji-Hoon Lee; Tanya T Paull
Journal: Methods Enzymol Date: 2006 Impact factor: 1.600

Review 5. gammaH2AX and MDC1: anchoring the DNA-damage-response machinery to broken chromosomes.

Authors: Manuel Stucki; Stephen P Jackson
Journal: DNA Repair (Amst) Date: 2006-03-10

6. Impaired DNA double strand break repair in cells from Nijmegen breakage syndrome patients.

Authors: Niall G Howlett; Zorica Scuric; Alan D D'Andrea; Robert H Schiestl
Journal: DNA Repair (Amst) Date: 2005-11-22

7. Identification of carboxyl-terminal MCM3 phosphorylation sites using polyreactive phosphospecific antibodies.

Authors: Yuling Shi; Gerald E Dodson; Partha S Mukhopadhyay; Naval P Shanware; Anthony T Trinh; Randal S Tibbetts
Journal: J Biol Chem Date: 2007-01-23 Impact factor: 5.157

8. Defective Mre11-dependent activation of Chk2 by ataxia telangiectasia mutated in colorectal carcinoma cells in response to replication-dependent DNA double strand breaks.

Authors: Haruyuki Takemura; V Ashutosh Rao; Olivier Sordet; Takahisa Furuta; Ze-Hong Miao; Linghua Meng; Hongliang Zhang; Yves Pommier
Journal: J Biol Chem Date: 2006-08-10 Impact factor: 5.157

9. ATM and ATR promote Mre11 dependent restart of collapsed replication forks and prevent accumulation of DNA breaks.

Authors: Kristina Trenz; Eloise Smith; Sarah Smith; Vincenzo Costanzo
Journal: EMBO J Date: 2006-04-06 Impact factor: 11.598

10. Autophosphorylation of DNA-PKCS regulates its dynamics at DNA double-strand breaks.

Authors: Naoya Uematsu; Eric Weterings; Ken-ichi Yano; Keiko Morotomi-Yano; Burkhard Jakob; Gisela Taucher-Scholz; Pierre-Olivier Mari; Dik C van Gent; Benjamin P C Chen; David J Chen
Journal: J Cell Biol Date: 2007-04-16 Impact factor: 10.539

24 in total

Review 1. ATM protein kinase: the linchpin of cellular defenses to stress.

Authors: Shahzad Bhatti; Sergei Kozlov; Ammad Ahmad Farooqi; Ali Naqi; Martin Lavin; Kum Kum Khanna
Journal: Cell Mol Life Sci Date: 2011-05-02 Impact factor: 9.261

2. ATM protein-dependent phosphorylation of Rad50 protein regulates DNA repair and cell cycle control.

Authors: Magtouf Gatei; Burkhard Jakob; Philip Chen; Amanda W Kijas; Olivier J Becherel; Nuri Gueven; Geoff Birrell; Ji-Hoon Lee; Tanya T Paull; Yaniv Lerenthal; Shazrul Fazry; Gisela Taucher-Scholz; Reinhard Kalb; Detlev Schindler; Regina Waltes; Thilo Dörk; Martin F Lavin
Journal: J Biol Chem Date: 2011-07-14 Impact factor: 5.157

PIKK-dependent phosphorylation of Mre11 induces MRN complex inactivation by disassembly from chromatin.

1. A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recovery.

2. Two-step activation of ATM by DNA and the Mre11-Rad50-Nbs1 complex.

Review 3. Signaling networks controlled by the MRN complex and MDC1 during early DNA damage responses.

4. Purification and biochemical characterization of ataxia-telangiectasia mutated and Mre11/Rad50/Nbs1.

Review 5. gammaH2AX and MDC1: anchoring the DNA-damage-response machinery to broken chromosomes.

6. Impaired DNA double strand break repair in cells from Nijmegen breakage syndrome patients.

7. Identification of carboxyl-terminal MCM3 phosphorylation sites using polyreactive phosphospecific antibodies.

8. Defective Mre11-dependent activation of Chk2 by ataxia telangiectasia mutated in colorectal carcinoma cells in response to replication-dependent DNA double strand breaks.

9. ATM and ATR promote Mre11 dependent restart of collapsed replication forks and prevent accumulation of DNA breaks.

10. Autophosphorylation of DNA-PKCS regulates its dynamics at DNA double-strand breaks.

Review 1. ATM protein kinase: the linchpin of cellular defenses to stress.

2. ATM protein-dependent phosphorylation of Rad50 protein regulates DNA repair and cell cycle control.

Review 3. The ATM protein kinase: regulating the cellular response to genotoxic stress, and more.

Review 4. Sharpening the ends for repair: mechanisms and regulation of DNA resection.

5. Plk1 Phosphorylation of Mre11 Antagonizes the DNA Damage Response.

6. Suppression of DNA-damage checkpoint signaling by Rsk-mediated phosphorylation of Mre11.

Review 7. Inhibiting the DNA damage response as a therapeutic manoeuvre in cancer.

8. ATP-driven Rad50 conformations regulate DNA tethering, end resection, and ATM checkpoint signaling.

9. Phosphorylation of Exo1 modulates homologous recombination repair of DNA double-strand breaks.

10. Monoketone analogs of curcumin, a new class of Fanconi anemia pathway inhibitors.