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Phosphorylation of EXO1 by CDKs 1 and 2 regulates DNA end resection and repair pathway choice.

Identifieur interne : 003715 ( PubMed/Curation ); précédent : 003714; suivant : 003716

Phosphorylation of EXO1 by CDKs 1 and 2 regulates DNA end resection and repair pathway choice.

Auteurs : Nozomi Tomimatsu [États-Unis] ; Bipasha Mukherjee [États-Unis] ; Molly Catherine Hardebeck [États-Unis] ; Mariya Ilcheva [États-Unis] ; Cristel Vanessa Camacho ; Janelle Louise Harris [Australie] ; Matthew Porteus [États-Unis] ; Bertrand Llorente [France] ; Kum Kum Khanna [Australie] ; Sandeep Burma [États-Unis]

Source :

Nature communications [ 2041-1723 ] ; 2014.

RBID : pubmed:24705021

Descripteurs français

English descriptors

KwdEn :
- Blotting, Western, Cell Line, Cell Line, Tumor, Cyclin-Dependent Kinase 2 (genetics), Cyclin-Dependent Kinase 2 (metabolism), Cyclin-Dependent Kinases (genetics), Cyclin-Dependent Kinases (metabolism), DNA Damage (genetics), DNA Damage (physiology), DNA Repair (genetics), DNA Repair (physiology), DNA Repair Enzymes (metabolism), Exodeoxyribonucleases (metabolism), Flow Cytometry, Fluorescent Antibody Technique, Humans, Immunoprecipitation, Phosphorylation (genetics), Phosphorylation (physiology).
MESH :
- chemical , genetics : Cyclin-Dependent Kinase 2, Cyclin-Dependent Kinases.
- chemical , metabolism : Cyclin-Dependent Kinase 2, Cyclin-Dependent Kinases, DNA Repair Enzymes, Exodeoxyribonucleases.
- genetics : DNA Damage, DNA Repair, Phosphorylation.
- physiology : DNA Damage, DNA Repair, Phosphorylation.
- Blotting, Western, Cell Line, Cell Line, Tumor, Flow Cytometry, Fluorescent Antibody Technique, Humans, Immunoprecipitation.

Abstract

Resection of DNA double-strand breaks (DSBs) is a pivotal step during which the choice between NHEJ and HR DNA repair pathways is made. Although CDKs are known to control initiation of resection, their role in regulating long-range resection remains elusive. Here we show that CDKs 1/2 phosphorylate the long-range resection nuclease EXO1 at four C-terminal S/TP sites during S/G2 phases of the cell cycle. Impairment of EXO1 phosphorylation attenuates resection, chromosomal integrity, cell survival and HR, but augments NHEJ upon DNA damage. In contrast, cells expressing phospho-mimic EXO1 are proficient in resection even after CDK inhibition and favour HR over NHEJ. Mutation of cyclin-binding sites on EXO1 attenuates CDK binding and EXO1 phosphorylation, causing a resection defect that can be rescued by phospho-mimic mutations. Mechanistically, phosphorylation of EXO1 augments its recruitment to DNA breaks possibly via interactions with BRCA1. In summary, phosphorylation of EXO1 by CDKs is a novel mechanism regulating repair pathway choice.

DOI: 10.1038/ncomms4561
PubMed: 24705021

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Cristel Vanessa Camacho

<affiliation><nlm:affiliation>1] Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, 2201 Inwood Road, NC7, 214E, Dallas, Texas 75390, USA [2].</nlm:affiliation>
<wicri:noCountry code="subField">USA [2]</wicri:noCountry>
</affiliation>

Le document en format XML

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<term>Cyclin-Dependent Kinases (genetics)</term>
<term>Cyclin-Dependent Kinases (metabolism)</term>
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<term>DNA Repair (physiology)</term>
<term>DNA Repair Enzymes (metabolism)</term>
<term>Exodeoxyribonucleases (metabolism)</term>
<term>Flow Cytometry</term>
<term>Fluorescent Antibody Technique</term>
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<term>Immunoprecipitation</term>
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<front><div type="abstract" xml:lang="en">Resection of DNA double-strand breaks (DSBs) is a pivotal step during which the choice between NHEJ and HR DNA repair pathways is made. Although CDKs are known to control initiation of resection, their role in regulating long-range resection remains elusive. Here we show that CDKs 1/2 phosphorylate the long-range resection nuclease EXO1 at four C-terminal S/TP sites during S/G2 phases of the cell cycle. Impairment of EXO1 phosphorylation attenuates resection, chromosomal integrity, cell survival and HR, but augments NHEJ upon DNA damage. In contrast, cells expressing phospho-mimic EXO1 are proficient in resection even after CDK inhibition and favour HR over NHEJ. Mutation of cyclin-binding sites on EXO1 attenuates CDK binding and EXO1 phosphorylation, causing a resection defect that can be rescued by phospho-mimic mutations. Mechanistically, phosphorylation of EXO1 augments its recruitment to DNA breaks possibly via interactions with BRCA1. In summary, phosphorylation of EXO1 by CDKs is a novel mechanism regulating repair pathway choice.</div>
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<Abstract><AbstractText>Resection of DNA double-strand breaks (DSBs) is a pivotal step during which the choice between NHEJ and HR DNA repair pathways is made. Although CDKs are known to control initiation of resection, their role in regulating long-range resection remains elusive. Here we show that CDKs 1/2 phosphorylate the long-range resection nuclease EXO1 at four C-terminal S/TP sites during S/G2 phases of the cell cycle. Impairment of EXO1 phosphorylation attenuates resection, chromosomal integrity, cell survival and HR, but augments NHEJ upon DNA damage. In contrast, cells expressing phospho-mimic EXO1 are proficient in resection even after CDK inhibition and favour HR over NHEJ. Mutation of cyclin-binding sites on EXO1 attenuates CDK binding and EXO1 phosphorylation, causing a resection defect that can be rescued by phospho-mimic mutations. Mechanistically, phosphorylation of EXO1 augments its recruitment to DNA breaks possibly via interactions with BRCA1. In summary, phosphorylation of EXO1 by CDKs is a novel mechanism regulating repair pathway choice.</AbstractText>
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<ForeName>Nozomi</ForeName>
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</AffiliationInfo>
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<CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>Cell. 2011 Apr 15;145(2):212-23</RefSource>
<PMID Version="1">21496642</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 2001 Jan 19;276(3):1993-7</RefSource>
<PMID Version="1">11067844</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Proteome Res. 2013 Jun 7;12(6):2414-21</RefSource>
<PMID Version="1">23312004</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>DNA Repair (Amst). 2011 Jan 2;10(1):73-86</RefSource>
<PMID Version="1">20970388</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Nat Rev Mol Cell Biol. 2010 Feb;11(2):138-48</RefSource>
<PMID Version="1">20029420</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>DNA Repair (Amst). 2012 Apr 1;11(4):441-8</RefSource>
<PMID Version="1">22326273</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Nature. 2009 May 21;459(7245):460-3</RefSource>
<PMID Version="1">19357644</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Genes Dev. 2011 Feb 15;25(4):350-62</RefSource>
<PMID Version="1">21325134</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Cell. 2010 Apr 16;141(2):243-54</RefSource>
<PMID Version="1">20362325</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Genes Dev. 2006 Jan 1;20(1):34-46</RefSource>
<PMID Version="1">16391231</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Nat Struct Mol Biol. 2010 Jan;17(1):11-6</RefSource>
<PMID Version="1">20051983</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>EMBO Rep. 2010 Dec;11(12):962-8</RefSource>
<PMID Version="1">21052091</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>EMBO Rep. 2009 Jun;10(6):629-35</RefSource>
<PMID Version="1">19444312</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Annu Rev Genet. 2006;40:363-83</RefSource>
<PMID Version="1">16895466</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 2003 Dec 19;278(51):50956-60</RefSource>
<PMID Version="1">14506259</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Mol Cell Biol. 2004 Nov;24(21):9478-86</RefSource>
<PMID Version="1">15485915</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>EMBO Rep. 2012 Jun;13(6):561-8</RefSource>
<PMID Version="1">22565321</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Nat Struct Mol Biol. 2011 Sep;18(9):1015-9</RefSource>
<PMID Version="1">21841787</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Mol Cell. 2013 Mar 7;49(5):840-1</RefSource>
<PMID Version="1">23473603</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>PLoS Genet. 2013;9(2):e1003277</RefSource>
<PMID Version="1">23468639</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Nat Struct Mol Biol. 2012 Feb;19(2):246-52</RefSource>
<PMID Version="1">22231403</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Front Genet. 2013 Jun 03;4:99</RefSource>
<PMID Version="1">23760669</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Genes Dev. 2006 Jul 1;20(13):1721-6</RefSource>
<PMID Version="1">16818604</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Mol Cell. 2013 Feb 21;49(4):657-67</RefSource>
<PMID Version="1">23273981</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Neoplasia. 2012 Jan;14(1):34-43</RefSource>
<PMID Version="1">22355272</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Genes Dev. 2008 Oct 15;22(20):2767-72</RefSource>
<PMID Version="1">18923075</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Nat Struct Mol Biol. 2010 Dec;17(12):1478-85</RefSource>
<PMID Version="1">21102445</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Cell Biol. 2006 Apr 24;173(2):195-206</RefSource>
<PMID Version="1">16618811</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Mol Cell. 2011 Mar 4;41(5):529-42</RefSource>
<PMID Version="1">21362549</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>DNA Repair (Amst). 2004 Dec 2;3(12):1549-59</RefSource>
<PMID Version="1">15474417</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Nature. 2008 Oct 9;455(7214):770-4</RefSource>
<PMID Version="1">18806779</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>DNA Repair (Amst). 2012 Mar 1;11(3):267-77</RefSource>
<PMID Version="1">22222486</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 2009 Apr 3;284(14):9558-65</RefSource>
<PMID Version="1">19202191</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Trends Biochem Sci. 2005 Nov;30(11):630-41</RefSource>
<PMID Version="1">16236519</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Mol Cancer Ther. 2009 Jul;8(7):1856-66</RefSource>
<PMID Version="1">19509270</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Eur J Biochem. 1997 Jan 15;243(1-2):527-36</RefSource>
<PMID Version="1">9030781</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Nucleic Acids Res. 2010 Apr;38(6):1821-31</RefSource>
<PMID Version="1">20019063</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Nucleic Acids Res. 2008 Feb;36(2):511-9</RefSource>
<PMID Version="1">18048416</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Nature. 2008 Oct 2;455(7213):689-92</RefSource>
<PMID Version="1">18716619</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Annu Rev Genet. 2011;45:247-71</RefSource>
<PMID Version="1">21910633</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Nature. 2012 Sep 27;489(7417):581-4</RefSource>
<PMID Version="1">22960744</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Exp Med. 2006 Feb 20;203(2):297-303</RefSource>
<PMID Version="1">16461339</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Cancer Res. 2010 Jul 1;70(13):5457-64</RefSource>
<PMID Version="1">20530668</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 2008 Mar 21;283(12):7713-20</RefSource>
<PMID Version="1">18171670</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Cancer Res. 2009 Mar 15;69(6):2663-8</RefSource>
<PMID Version="1">19276368</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Cell. 2008 Sep 19;134(6):981-94</RefSource>
<PMID Version="1">18805091</PMID>
</CommentsCorrections>
</CommentsCorrectionsList>
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	Serveur d'exploration sur les relations entre la France et l'Australie
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Phosphorylation of EXO1 by CDKs 1 and 2 regulates DNA end resection and repair pathway choice.

Phosphorylation of EXO1 by CDKs 1 and 2 regulates DNA end resection and repair pathway choice.

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